Method and reagent for inhibiting hepatitis C virus replication

ABSTRACT

An enzymatic RNA molecule which specifically cleaves RNA of a hepatitis C virus.

This is a continuation of application Ser. No. 08/182,968 filed Jan. 13, 1994 hereby incorporated by reference in its totality (including drawings), now U.S. Pat. No. 5,610,054, which is a continuation-in-part of Draper, entitled "Method and Reagent For Inhibiting Hepatitis C Virus Replication", filed May 14, 1992, assigned U.S. Ser. No. 07/882,888, now abandoned, the whole of which is hereby incorporated by reference herein.

BACKGROUND OF THE INVENTION

This invention relates to reagents useful as inhibitors of hepatitis C virus (HCV) replication and gene expression.

The following is a discussion of relevant art, none of which is admitted to be prior art to the pending claims.

The Hepatitis C virus group is responsible for most cases of non-A, non-B hepatitis. Although non-A, non-B hepatitis may be caused by many different viruses, the principal cause is HCV. The infection is transmitted through blood transfusions (25-50% of hemophiliacs have chronic hepatitis), percutaneous infusion from illicit drug usage (25-50% of all drug users have non-A, non-B hepatitis), renal organ transplant (where most late mortality is due to non-A, non-B hepatitis), and maternal-neonatal transfer. Up to 20% of sporadic outbreaks of hepatitis are caused by HCV.

The association of hepatitis C virus in posttransfusion hepatitis (>95% of the cases) and the subsequent observation that infection with this virus, more so than with hepatitis B virus, correlates strongly with the development of hepatocellular carcinoma and liver cirrhosis has led to intense study of the molecular biology of the viral genes.

Hepatitis C virus (HCV) is a positive-stranded, enveloped virus which is evolutionarily related to the flaviviruses and pestiviruses. The HCV genome consists of a 5' untranslated region (5' UTR), a long open reading frame of between 9030 and 9099 nucleotides and a 3' UTR. The 3' end of the genome has been reported to contain a short stretch of poly(A) in type I strains, but this has not been confirmed in type II, III or IV strains. It has been reported that sequences in the 5' UTR exhibit negative translational control over viral gene expression, but the major regulation of HCV gene expression comes from the proteolytic clevages of the polyprotein. Various proteolytic cleavages of the polyprotein are essential for the efficient expression of replication-associated viral proteins after translation. The resultant replicase proteins interact with a region of between 27 and 45 nucleotides in the 3' UTR which functions as a structural cue for the initiation of viral genomic replication.

Cleavage of the polyprotein of HCV uses both cellular and virally-encoded proteases and generates at least nine proteins. A tenth viral protein (a second protease) has been reported to be generated by alternative cleavage of the polyprotein, but has not been confirmed. Confirmed virally-encoded proteins can be classified as structural or non-structural proteins. The structural proteins of the virus are the C protein (22 kD), E glycoprotein (35 kD) and the E2/NS1 glycoprotein (58 kD). The non-structural proteins include the NS2 (53 kD), NS3 (70 kD), NS4a (8 kD), NS4b (27 kD), NS5a (58 kD) and NS5b (68 kD).

The C protein is a hydrophobic protein which constitutes the core structural component of the viral particle and may play a role in localizing the viral particle to the cellular membrane. There is also evidence from transient assays that the core protein may function as a transactivator of gene expression. This protein is essential to viral replication and appears to be highly conserved at the nucletide level of homology among known types of HCV.

The envelope proteins are necessary for viral replication but their nucleotide (and amino acid) sequences diverge significantly between types of HCV. The NS3 protein functions as the major viral protease and mutations in this protein lead to inactivation of viral replication by inhibiting the processing of the polyprotein. The nucleotide sequence of the NS3 region is highly conserved among viral isolates.

The level of infidelity exhibited by the HCV RNA replicase has been indirectly quantified by assessing the sequential appearance of nucleotide substitutions in the genomes of HCV samples obtained from the same patient. These studies suggested that the nucleotide divergence was minimal but it may have been an underestimate of the actual infidelity of the replicase because the recovered samples were actually pre-selected by growth in the patient. Unacceptible substitutions would have been lost during the outgrowth of the virus.

The replication of HCV in hepatocytes is integrally intertwined with the replication of other hepatitis viruses. Although hepatitis delta virus (HDV) is quite distinct from HCV, the life cycles of the two viruses can be interdependent. Normally HDV depends upon the replication of Hepatitis B Virus (HBV) to supply capsid proteins and other functions necessary for the assembly of infectious HDV particles. Because HCV inhibits HBV and Hepatitis A virus (HAV) growth in co-infected cells, the replication of HCV can also inhibit the maturation of HDV. The use of HDV as a gene vector for treatment of HCV infections would not be influenced by this interference because gene expression of the HDV genome is apparently uninhibited by HCV.

SUMMARY OF THE INVENTION

The invention features novel enzymatic RNA molecules, or ribozymes, and methods for their use for inhibiting HCV replication. Such ribozymes can be used in a method for treatment of diseases caused by these related viruses in man and other animals, including other primates.

Ribozymes are RNA molecules having an enzymatic activity which is able to repeatedly cleave other separate RNA molecules in a nucleotide base sequence specific manner. Such enzymatic RNA molecules can be targeted to virtually any RNA transcript, and efficient cleavage achieved in vitro. Kim et al., 84 Proc. Nat. Acad. of Sci. USA 8788, 1987, Hazeloff et al., 234 Nature 585, 1988, Cech, 260 JAMA 3030, 1988, and Jefferies et al., 17 Nucleic Acid Research 1371, 1989.

Ribozymes act by first binding to a target RNA. Such binding occurs through the target RNA binding portion of a ribozyme which is held in close proximity to an enzymatic portion of the RNA which acts to cleave the target RNA. Thus, the ribozyme first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After a ribozyme has bound and cleaved its RNA target it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.

The enzymatic nature of a ribozyme is advantageous over other technologies, such as antisense technology (where a nucleic acid molecule simply binds to a nucleic acid target to block its translation) since the effective concentration of ribozyme necessary to effect a therapeutic treatment is lower than that of an antisense oligonucleotide. This advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor, with the specificity of inhibition depending not only on the base pairing mechanism of binding, but also on the mechanism by which the molecule inhibits the expression of the RNA to which it binds. That is, the inhibition is caused by cleavage of the RNA target and so specificity is defined as the ratio of the rate of cleavage of the targeted RNA over the rate of cleavage of non-targeted RNA. This cleavage mechanism is dependent upon factors additional to those involved in base pairing. Thus, it is thought that the specificity of action of a ribozyme is greater than that of antisense oligonucleotide binding the same RNA site.

This class of chemical cleavers will exhibit a high degree of specificity for only the viral mRNA in infected cells. A ribozyme molecule targeted to a highly conserved sequence region will allow the treatment of many strains of human HCV with a single compound. No treatment exists which specifically attacks expression of the viral gene(s) of HCV. Current treatment protocols (interferon and ribavirin) consist of treating the symptoms of the disease, not the viral replication. Upon cessation of current treatment protocols, a rebound of disease ensues because the treatment does not impact the latency of the virus or actual viral replication. The cleavage of viral RNA offers a novel treatment which will reduce virus replication and establishment of latency in newly infected cells.

The methods of this invention can be used to treat human hepatitis C virus infections, which include both acute and chronic virus infection and HCV-induced hepatocyte transformation. The utility can be extended to other species of HCV which infect non-human animals, where such infections are of veterinary importance. Further, the utility may be extended to other members of the pestivirus and flavivirus families.

Treatment will occur at the time of active viral infection and will reduce virus loads in the infected cells and also disable viral replication. Ribozyme treatment may also be used as a means of creating defective genomes which can be used in vaccines.

Thus, in the first aspect the invention features an enzymatic RNA molecule (or ribozyme) which specifically cleaves HCV RNA.

Preferred cleavage sites are within regions required for viral replication, e.g., protein synthesis, such as the 5' non-translated region of the HCV genome. This region is believed to control the translation of viral proteins in a manner which is reminiscent of the cap independent translational control of picornaviruses. Disruption of this region in the RNA results in deficient protein synthesis as well as incomplete DNA synthesis (and inhibition of transcription from the defective genomes).

Alternative regions outside of the 5' non-translated region also make suitable targets of ribozyme-mediated inhibition of HCV replication. Such targets include the genomic regions which encode the viral structural protein, E2/NS1, and the regions encoding the nonstructural proteins, especially the NS3 protease and NS2/NS3 hybrid proteases. Selection of particular target regions will depend upon the secondary structure of the genome. To avoid the potential of viral escape from ribozyme therapy, by random base changes in the genomic RNA, targeting of multiple regions within the 5' UTR, or the C and NS3 genes is anticipated. Multiple targeting will also minimize the ability of the virus to utilize point mutations for escape from immune surveillance. The phase variation which accompanies amino acid substitutions in the surface proteins (and result from point mutations in the genome of HCV) has been proposed to account for the viral persistance which is typical of HCV infections. Thus, two or more different ribozymes can be used in this invention for therapeutic treatment.

By "gene" is meant to refer to either the protein coding regions of the cognate mRNA, or any regulatory regions in the RNA which regulate synthesis of the protein or stability of the mRNA.

By "enzymatic RNA molecule" it is meant an RNA molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave RNA in that target. That is, the enzymatic RNA molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. This complementarity functions to allow sufficient hybridization of the enzymatic RNA molecule to the target RNA to allow the cleavage to occur. 100% complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. By "equivalent" RNA to HCV is meant to include those naturally occurring RNA molecules associated with viral caused diseases in various animals, including humans, and other primates. These viral RNAs have similar structures and equivalent genes to each other.

In preferred embodiments, the enzymatic RNA molecule is formed in a hammerhead motif, but may also be formed in the motif of a hairpin, hepatitis delta virus, group I intron or RNaseP RNA (in association with an RNA guide sequence). Examples of such hammerhead motifs are described by Rossi et al., 8 AIDS RESEARCH AND HUMAN RETROVIRUSES 183, 1992, of hairpin motifs by Hampel et al., RNA CATALYST FOR CLEAVING SPECIFIC RNA SEQUENCES, filed Sep. 20, 1989, which is a continuation-in-part of U.S. Ser. No. 07/247,100 filed Sep. 20, 1988, Hampel and Tritz, 28 Biochemistry 4929, 1989 and Hampel et al., 18 Nucleic Acids Research 299, 1990, and an example of the hepatitis delta virus motif is described by Perrotta and Been, 31 Biochemistry 16, 1992, of the RNaseP motif by Guerrier-Takada et al., 35 Cell 849, 1983, and of the group I intron by Cech et al., U.S. Pat. No. 4,987,071. These specific motifs are not limiting in the invention and those skilled in the art will recognize that all that is important in an enzymatic RNA molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule.

In particularly preferred embodiments, the RNA which is cleaved by the ribozyme is in the 5' UTR of HCV genomic RNA or in the C protein or NS3 ORFs. Nucleotide numbers in the HCV genome are given to delineate the 5' ends of the target regions. Primary sequence data is taken from Tanaka et al, 23 Virus Res. 39, 1992. For comparison, the HCV sequence data of Choo et al 88 Proc. Natl. Acad. Sci. USA 2451 1991 was used.

                  TABLE 1     ______________________________________     HCV mRNA target sequences.     Nucleotide No.              Target Sequence.sup.a                                  Seq. ID. NO.     ______________________________________      27      CGACACU C CACCAUA   Seq. ID. NO. 001      114     GCAGCCU C CAGGACC   Seq. ID. NO. 002      128     CCCCCCU C CCGGGAG   Seq. ID. NO. 003      148     UAGUGGU C UGCGGAA   Seq. ID. NO. 004      165     GGUGAGU A CACCGGA   Seq. ID. NO. 005      175     CCGGAAU U GCCAGGA   Seq. ID. NO. 006      199     CCUUUCU U GGAUCAA   Seq. ID. NO. 007      213     ACCCGCU C AAUGCCU   Seq. ID. NO. 008      252     GACUGCU A GCCGAGU   seq. ID. NO. 009      260     GCCGAGU A GUGUUGG   Seq. ID. NO. 010      265     GUAGUGU U GGGUCGC   Seq. ID. NO. 011      270     GUUGGGU C GCGAAAG   Seq. ID. NO. 012      288     UUGUGGU A CUGCCUG   Seq. ID. NO. 013      298     GCCUGAU A GGGUGCU   Seq. ID. NO. 014      306     GGGUGCU U GCGAGUG   Seq. ID. NO. 015      325     GGGAGGU C UCGUAGA   Seq. ID. NO. 016      327     GAGGUCU C GUAGACC   Seq. ID. NO. 017      330     GUCUCGU A GACCGUG   Seq. ID. NO. 018      407     AGGACGU C AAGUUCC   Seq. ID. NO. 019      412     GUCAAGU U CCCGGGC   Seq. ID. NO. 020      413     UCAAGUU C CCGGGCG   Seq. ID. NO. 021      426     CGGUGGU C AGAUCGU   Seq. ID. NO. 022      472     CCCACGU U GGGUGUG   Seq. ID. NO. 023      489     CGCGACU A GGAAGAC   Seq. ID. NO. 024      498     GAAGACU U CCGAACG   Seq. ID. NO. 025      499     AAGACUU C CGAACGG   Seq. ID. NO. 026      508     GAACGGU C GCAACCU   Seq. ID. NO. 027      534     ACAACCU A UCCCCAA   Seq. ID. NO. 028      536     AACCUAU C CCCAAGG   Seq. ID. NO. 029      546     CAAGGCU C GCCGACC   Seq. ID. NO. 030      561     CGAGGGU A GGGCCUG   Seq. ID. NO. 031      573     CUGGGCU C AGCCUGG   Seq. ID. NO. 032      583     CCUGGGU A CCCUUGG   Seq. ID. NO. 033      588     GUACCCU U GGCCCCU   Seq. ID. NO. 034      596     GGCCCCU C UAUGGCA   Seq. ID. NO. 035      598     CCCCUCU A UGGCAAU   Seq. ID. NO. 036      632     GAUGGCU C CUGUCAC   Seq. ID. NO. 037      637     CUCCUGU C ACCCCGC   Seq. ID. NO. 038      649     CGCGGCU C CCGGCCU   Seq. ID. NO. 039      657     CCGGCCU A GUUGGGG   Seq. ID. NO. 040      660     GCCUAGU U GGGGCCC   Seq. ID. NO. 041      696     GCGCAAU C UGGGUAA   Seq. ID. NO. 042      707     GUAAGGU C AUCGAUA   Seq. ID. NO. 043      710     AGGUCAU C GAUACCC   Seq. ID. NO. 044      714     CAUCGAU A CCCUCAC   Seq. ID. NO. 045      730     UGCGGCU U CGCCGAC   Seq. ID. NO. 046      731     GCGGCUU C GCCGACC   Seq. ID. NO. 047      748     AUGGGGU A CAUUCCG   Seq. ID. NO. 048      752     GGUACAU U CCGCUCG   Seq. ID. NO. 049      753     GUACAUU C CGCUCGU   Seq. ID. NO. 050      758     UUCCGCU C GUCGGCG   Seq. ID. NO. 051      761     CGCUCGU C GGCGCCC   Seq. ID. NO. 052      773     CCCCCCU A GGGGGCG   Seq. ID. NO. 053      806     AUGGUGU C CGGGUUC   Seq. ID. NO. 054      812     UCCGGGU U CUGGAGG   Seq. ID. NO. 055      813     CCGGGUU C UGGAGGA   Seq. ID. NO. 056      832     GUGAACU A CGCAACA   Seq. ID. NO. 057      847     GGGAACU U GCCCGGU   Seq. ID. NO. 058      855     GCCCGGU U GCUCUUU   Seq. ID. NO. 059      859     GGUUGCU C UUUCUCU   Seq. ID. NO. 060      982     AUUGUGU A UGAGGCA   Seq. ID. NO. 061     1001     GCAUGAU C AUGCAUA   Seq. ID. NO. 062     1022     GGUGCGU A CCCUGCG   Seq. ID. NO. 063     1031     CCUGCGU U CGGGAGA   Seq. ID. NO. 064     1032     CUGCGUU C GGGAGAA   Seq. ID. NO. 065     1048     AACGCCU C CCGUUGU   Seq. ID. NO. 066     1053     CUCCCGU U GUUGGGU   Seq. ID. NO. 067     1056     CCGUUGU U GGGUAGC   Seq. ID. NO. 068     1061     GUUGGGU A GCGCUCA   Seq. ID. NO. 069     1127     GCCACGU C GACUUGC   Seq. ID. NO. 070     1132     GUCGACU U GCUCGUU   Seq; ID. NO. 071     1136     ACUUGCU C GUUGGGG   Seq. ID. NO. 072     1139     UGCUCGU U GGGGCGG   Seq. ID. NO. 073     1153     GCCGCUU U CUGUUCC   Seq. ID. NO. 074     1154     CCGCUUU C UGUUCCG   Seq. ID. NO. 075     1158     UUUCUGU U CCGCCAU   Seq. ID. NO. 076     1159     UUCUGUU C CGCCAUG   Seq. ID. NO. 077     1168     GCCAUGU A CGUGGGG   Seq. ID. NO. 078     1189     UGCGGAU C CGUUUUC   Seq. ID. NO. 079     1193     GAUCCGU U UUCCUCG   Seq. ID. NO. 080     1194     AUCCGUU U UCCUCGU   Seq. ID. NO. 081     1195     UCCGUUU U CCUCGUC   Seq. ID. NO. 082     1196     CCGUUUU C CUCGUCU   Seq. ID. NO. 083     1280     GCCAUGU A UCAGGUC   Seq. ID. NO. 084     1282     CAUGUAU C AGGUCAC   Seq. ID. NO. 085     1287     AUCAGGU C ACCGCAU   Seq. ID. NO. 086     1373     AAGCUGU C GUGGAUA   Seq. ID. NO. 087     1380     CGUGGAU A UGGUGGC   Seq. ID. NO. 088     1406     GGGGAGU C CUAGCGG   Seq. ID. NO. 089     1409     GAGUCCU A GCGGGCC   Seq. ID. NO. 090     1418     CGGGCCU U GCCUACU   Seq. ID. NO. 091     1423     CUUGCCU A CUAUUCC   Seq. ID. NO. 092     1426     GCCUACU A UUCCAUG   Seq. ID. NO. 093     1428     CUACUAU U CCAUGGU   Seq. ID. NO. 094     1429     UACUAUU C CAUGGUG   Seq. ID. NO. 095     1727     GCUCCAU C GACAAGU   Seq. ID. NO. 096     1735     GACAAGU U CGCUCAG   Seq. ID. NO. 097     1736     ACAAGUU C GCUCAGG   Seq. ID. NO. 098     1740     GUUCGCU C AGGGAUG   Seq. ID. NO. 099     1757     GCCCCAU C ACCUAUA   Seq. ID. NO. 100     1762     AUCACCU A UACCGAG   Seq. ID. NO. 101     1795     AGGCCUU A CUGCUGG   Seq. ID. NO. 102     1806     CUGGCAU U ACGCACC   Seq. ID. NO. 103     1807     UGGCAUU A CGCACCU   Seq. ID. NO. 104     1815     CGCACCU C GGCAGUG   Seq. ID. NO. 105     1827     GUGUGGU A UCGUACC   Seq. ID. NO. 106     1829     GUGGUAU C GUACCUG   Seq. ID. NO. 107     1832     GUAUCGU A CCUGCGU   Seq. ID. NO. 108     1840     CCUGCGU C GCAGGUG   Seq. ID. NO. 109     1854     GUGUGGU C CAGUGUA   Seq. ID. NO. 110     1883     GCCCUGU U GUAGUGG   Seq. ID. NO. 111     1886     CUGUUGU A GUGGGGA   Seq. ID. NO. 112     1902     GACCGAU C GGUCCGG   Seq. ID. NO. 113     1906     GAUCGGU C CGGUGCC   Seq. ID. NO. 114     1917     UGCCCCU A CGUAUAA   Seq. ID. NO. 115     1921     CCUACGU A UAACUGG   Seq. ID. NO. 116     1923     UACGUAU A ACUGGGG   Seq. ID. NO. 117     1990     AACUGGU U UGGCUGU   Seq. ID. NO. 118     1991     ACUGGUU U GGCUGUA   Seq. ID. NO. 119     1998     UGGCUGU A CAUGGAU   Seq. ID. NO. 120     2043     GGGCCCU C CGUGCAA   Seq. ID. NO. 121     2054     GCAACAU C GGGGGGG   Seq. ID. NO. 122     2063     GGGGGGU C GGCAACC   Seq. ID. NO. 123     2072     GCAACCU C ACCUUGA   Seq. ID. NO. 124     2077     CUCACCU U GACCUGC   Seq. ID. NO. 125     2121     GGCCACU U ACACAAA   Seq. ID. NO. 126     2122     GCCACUU A CACAAAA   Seq. ID. NO. 127     2137     UGUGGCU C GGGGCCA   Seq. ID. NO. 128     2149     CCAUGGU U AACACCU   Seq. ID. NO. 129     2150     CAUGGUU A ACACCUA   Seq. ID. NO. 130     2219     UUACCAU C UUUAAGG   Seq. ID. NO. 131     2221     ACCAUCU U UAAGGUU   Seq. ID. NO. 132     2261     ACAGGCU U AGUGCUG   Seq. ID. NO. 133     2262     CAGGCUU A GUGCUGC   Seq. ID. NO. 134     2295     AGAGCGU U GCGACCU   Seq. ID. NO. 135     2320     GACAGAU C GGAGCUC   Seq. ID. NO. 136     2327     CGGAGCU C AGCCCGC   Seq. ID. NO. 137     2344     CUGCUGU C CACGACA   Seq. ID. NO. 138     2417     UCCACCU C CAUCAGA   Seq. ID. NO. 139     2421     CCUCCAU C AGAACAU   Seq. ID. NO. 140     2429     AGAACAU C GUGGACG   Seq. ID. NO. 141     2534.    CGCGCGU C UGUGCCU   Seq. ID. NO. 145     2585     CCGCCCU A GAGAACC   Seq. ID. NO. 143     2600     UGGUGGU C CUCAACG   Seq. ID. NO. 144     2603     UGGUCCU C AACGCGG   Seq. ID. NO. 145     2671     GCCUGGU A CAUCAAG   Seq. ID. NO. 146     2675     GGUACAU C AAGGGCA   Seq. ID. NO. 147     2690     GGCUGGU C CCUGGGG   Seq. ID. NO. 148     2704     GCGGCAU A UGCUCUG   Seq. ID. NO. 149     2709     AUAUGCU C UGUACGG   Seq. ID. NO. 150     2713     GCUCUGU A CGGCGUG   Seq. ID. NO. 151     2738     UCCUGCU C CUGCUGG   Seq. ID. NO. 152     2763     ACGGGCU U ACGCCAU   Seq. ID. NO. 153     2764     CGGGCUU A CGCCAUG   Seq. ID. NO. 154     2878     UGGUGGU U ACAAUAC   Seq. ID. NO. 155     2879     GGUGGUU A CAAUACU   Seq. ID. NO. 156     2884     UUACAAU A CUUUAUC   Seq. ID. NO. 157     2887     CAAUACU U UAUCACC   Seq. ID. NO. 158     2888     AAUACUU U AUCACCA   Seq. ID. NO. 159     2910     GGCGCAU U UGUGCGU   Seq. ID. NO. 160     2911     GCGCAUU U GUGCGUG   Seq. ID. NO. 161     2924     UGUGGGU C CCCCCUC   Seq. ID. NO. 162     2931     CCCCCCU C UCAAUGU   Seq. ID. NO. 163     2933     CCCCUCU C AAUGUCC   Seq. ID. NO. 164     2939     UCAAUGU C CGGGGGG   Seq. ID. NO. 165     2958     CGAUGCU A UCAUCCU   Seq. ID. NO. 166     2960     AUGCUAU C AUCCUCC   Seq. ID. NO. 167     2963     CUAUCAU C CUCCUCA   Seq. ID. NO. 168     2966     UCAUCCU C CUCACAU   Seq. ID. NO. 169     2969     UCCUCCU C ACAUGUG   Seq. ID. NO. 170     3059     CUGCCAU A ACUGCGA   Seq. ID. NO. 171     3138     AGGCCAU U ACGUCCA   Seq. ID. NO. 172     3139     GGCCAUU A CGUCCAA   Seq. ID. NO. 173     3143     AUUACGU C CAAAUGG   Seq. ID. NO. 174     3154     AUGGCCU U CAUGAAG   Seq. ID. NO. 175     3155     UGGCCUU C AUGAAGC   Seq. ID. NO. 176     3209     CCCCGCU A CAGGAUU   Seq. ID. NO. 177     3216     ACAGGAU U GGGCCCA   Seq. ID. NO. 178     3233     CGGGCCU A CGAGACC   Seq. ID. NO. 179     3242     GAGACCU U GCGGUGG   Seq. ID. NO. 180     3263     AGCCCGU C GUCUUCU   Seq. ID. NO. 181     3266     CCGUCGU C UUCUCUG   Seq. ID. NO. 182     3268     GUCGUCU U CUCUGAC   Seq. ID. NO. 183     3290     CCAAGAU C AUCACCU   Seq. ID. NO. 184     3293     AGAUCAU C ACCUGGG   Seq. ID. NO. 185     3329     GGGACAU C AUCUUGG   Seq. ID. NO. 186     3332     ACAUCAU C UUGGGAC   Seq. ID. NO. 187     3334     AUCAUCU U GGGACUG   Seq. ID. NO. 188     3347     UGCCCGU C UCCGCCC   Seq. ID. NO. 189     3349     CCCGUCU C CGCCCGA   Seq. ID. NO. 190     3371     GGGAGAU A CUUCUGG   Seq. ID. NO. 191     3416     GGCGACU C CUUGCCC   Seq. ID. NO. 192     3419     GACUCCU U GCCCCCA   Seq. ID. NO. 193     3428     CCCCCAU C ACGGCCU   Seq. ID. NO. 194     3482     CUAGCCU C ACAGGCC   Seq. ID. NO. 195     3518     GGGAGGU U CAAGUGG   Seq. ID. NO. 196     3519     GGAGGUU C AAGUGGU   Seq. ID. NO. 197     3527     AAGUGGU U UCCACCG   Seq. ID. NO. 198     3528     AGUGGUU U CCACCGC   Seq. ID. NO. 199     3529     GUGGUUU C CACCGCA   Seq. ID. NO. 200     3576     UGUGUGU U GGACCGU   Seq. ID. NO. 201     3601     GCCGGCU C AAAGACC   Seq. ID. NO. 202     3614     AGACCCU A GCCGGCC   Seq. ID. NO. 203     3684     UGCGCCU C CCGGGGC   Seq. ID. NO. 204     3696     GGCGCGU U CCCUUAC   Seq. ID. NO. 205     3697     GCGCGUU C CCUUACA   Seq. ID. NO. 206     3701     GUUCCCU U ACACCAU   Seq. ID. NO. 207     3702     UUCCCUU A CACCAUG   Seq. ID. NO. 208     3724     GGUAGCU C GGACCUC   Seq. ID. NO. 209     3731     CGGACCU C UAUCUGG   Seq. ID. NO. 210     3733     GACCUCU A UCUGGUC   Seq. ID. NO. 211     3735     CCUCUAU C UGGUCAC   Seq. ID. NO. 212     3740     AUCUGGU C ACGAGAC   Seq. ID. NO. 213     3761     ACGUCAU U CCGGUGC   Seq. ID. NO. 214     3762     CGUCAUU C CGGUGCG   Seq. ID. NO. 215     3786     UGACGGU C GGGGGAG   Seq. ID. NO. 216     3797     GGAGCCU A CUGUCCC   Seq. ID. NO. 217     3802     CUACUGU C CCCCAGA   Seq. ID. NO. 218     3835     GGCUCUU C GGGUGGC   Seq. ID. NO. 219     3851     CACUGCU C UGCCCUU   Seq. ID. NO. 220     3858     CUGCCCU U CGGGGCA   Seq. ID. NO. 221     3859     UGCCCUU C GGGGCAC   Seq. ID. NO. 222     3872     ACGCUGU A GGCAUCU   Seq. ID. NO. 223     3878     UAGGCAU C UUCCGGG   Seq. ID. NO. 224     3880     GGCAUCU U CCGGGCU   Seq. ID. NO. 225     3881     GCAUCUU C CGGGCUG   Seq. ID. NO. 226     3908     GGGGGGU U GCGAAGG   Seq. ID. NO. 227     4056     GAGCACU A AAGUGCC   Seq. ID. NO. 228     4072     GCUGCGU A CGCAGCC   Seq. ID. NO. 229     4087     CAAGGGU A CAAGGUA   Seq. ID. NO. 230     4115     CAUCUGU U GCCGCCA   Seq. ID. NO. 231     4175     CCAACAU C AGAACUG   Seq. ID. NO. 232     4187     CUGGGGU A AGGACCA   Seq. ID. NO. 233     4228     UCCACCU A UGGUAAG   Seq. ID. NO. 234     4233     CUAUGGU A AGUUCCU   Seq. ID. NO. 235     4237     GGUAAGU U CCUUGCC   Seq. ID. NO. 236     4238     GUAAGUU C CUUGCCG   Seq. ID. NO. 237     4241     AGUUCCU U GCCGACG   Seq. ID. NO. 238     4280     AUAUCAU A AUAUGUG   Seq. ID. NO. 239     4283     UCAUAAU A UGUGAUG   Seq. ID. NO. 240     4337     GCACAGU C CUGGACC   Seq. ID. NO. 241     4370     CGCGGCU C GUCGUGC   Seq. ID. NO. 242     4373     GGCUCGU C GUGCUCG   Seq. ID. NO. 243     4379     UCGUGCU C GCCACCG   Seq. ID. NO. 244     4425     CCCAAAU A UUGAGGA   Seq. ID. NO. 245     4444     GCUCUGU C CAACACU   Seq. ID. NO. 246     4460     GAGAGAU C CCCUUCU   Seq. ID. NO. 243     4481     AGGCCAU C CCCCUGG   Seq. ID. NO. 248     4487     UCCCCCU C GAGGCCA   Seq. ID. NO. 249     4496     AGGCCAU C AAGGGGG   Seq. ID. NO. 250     4528     UGCCACU C CAAGAAG   Seq. ID. NO. 251     4577     UCGGAAU C AAUGCCG   Seq. ID. NO. 252     4586     AUGCCGU A GCGUAUU   Seq. ID. NO. 253     4591     GUAGCGU A UUACCGG   Seq. ID. NO. 254     4593     AGCGUAU U ACCGGGG   Seq. ID. NO. 255     4594     GCGUAUU A CCGGGGU   Seq. ID. NO. 256     4616     UGUCCGU C AUACCGA   Seq. ID. NO. 257     4619     CCGUCAU A CCGACUA   Seq. ID. NO. 258     4626     ACCGACU A GCGGAGA   Seq. ID. NO. 259     4672     ACGGGCU A CACCGGU   Seq. ID. NO. 260     4697     CGGUGAU C GACUGCA   Seq. ID. NO. 261     4789     GCGGUGU C GCGCUCA   Seq. ID. NO. 162     4795     UCGCGCU C ACAACGG   Seq. ID. NO. 263     4920     CUGUGCU U GGUAUGA   Seq. ID. NO. 264     4924     GCUUGGU A UGAGCUC   Seq. ID. NO. 265     4931     AUGAGCU C ACGCCCG   Seq. ID. NO. 266     4947     UGAGACU A CAGUCAG   Seq. ID. NO. 267     4952     CUACAGU C AGGUUGC   Seq. ID. NO. 268     4957     GUCAGGU U GCGGGCU   Seq. ID. NO. 269     4965     GCGGGCU U ACCUGAA   Seq. ID. NO. 270     4966     CGGGCUU A CCUGAAU   Seq. ID. NO. 271     4974     CCUGAAU A CACCAGG   Seq. ID. NO. 272     4984     CCAGGGU U GCCCGUC   Seq. ID. NO. 273     4991     UGCCCGU C UGCCAGG   Seq. ID. NO. 274     5004     GGACCAU C UGGAGUU   Seq. ID. NO. 275     5102     ACCUGGU A GCAUACC   Seq. ID. NO. 276     5107     GUAGCAU A CCAAGCC   Seq. ID. NO. 277     5133     CAGGGCU C AGGCUCC   Seq. ID. NO. 278     5218     CUGCUGU A UAGGCUA   Seq. ID. NO. 279     5220     GCUGUAU A GGCUAGG   Seq. ID. NO. 280     5306     UGGAGGU C GUCACUA   Seq. ID. NO. 281     5309     AGGUCGU C ACUAGCA   Seq. ID. NO. 282     5313     CGUCACU A GCACCUG   Seq. ID. NO. 283     5330     UGCUGGU A GGCGGAG   Seq. ID. NO. 284     5339     GCGGAGU C CUUGCAG   Seq. ID. NO. 285     5342     GAGUCCU U GCAGCUC   Seq. ID. NO. 286     5359     GCCGCAU A UUGCCUG   Seq. ID. NO. 287     5361     CGCAUAU U GCCUGAC   Seq. ID. NO. 288     5376     AACCGGU A GUGUGGU   Seq. ID. NO. 289     5399     GUAGGAU C AUUUUGU   Seq. ID. NO. 290     5423     CGGCUGU U GUUCCCG   Seq. ID. NO. 291     5426     CUGUUGU U CCCGACA   Seq. ID. NO. 292     5427     UGUUGUU C CCGACAG   Seq. ID. NO. 293     5524     GAGCAGU U CAAGCAG   Seq. ID. NO. 294     5525     AGCAGUU C AAGCAGA   Seq. ID. NO. 295     5583     CGCUGCU C CCGUGGU   Seq. ID. NO. 296     5596     GUGGAGU C CAGGUGG   Seq. ID. NO. 297     5612     GGGCCCU U GAGGCUU   Seq. ID. NO. 298     5620     GAGGCCU U CUGGGCA   Seq. ID. NO. 299     5621     AGGCCUU C UGGGCAA   Seq. ID. NO. 300     5674     GCAGGCU U AUCCACU   Seq. ID. NO. 301     5675     CAGGCUU A UCCACUC   Seq. ID. NO. 302     5767     CUCCUGU U CAACAUC   Seq. ID. NO. 303     5768     UCCUGUU C AACAUCU   Seq. ID. NO. 304     5801     CUCAACU C GCUCCUC   Seq. ID. NO. 305     5805     ACUCGCU C CUCCCAG   Seq. ID. NO. 306     5821     GCUGCUU C GGCCUUC   Seq. ID. NO. 307     5827     UCGGCCU U CGUGGGC   Seq. ID. NO. 308     5828     CGGCCUU C GUGGGCG   Seq. ID. NO. 309     5843     CCGGCAU U GCCGGUG   Seq. ID. NO. 310     5858     CGGCCAU U GGCAGCA   Seq. ID. NO. 311     5867     GCAGCAU A GGCCUUG   Seq. ID. NO. 312     5873     UAGGCCU U GGGAAGG   Seq. ID. NO. 313     5905     GCGGGCU A UGGAGCG   Seq. ID. NO. 314     5930     GUGCACU C GUGGCUU   Seq. ID. NO. 315     5937     GCUGGCU U UUAAGGU   Seq. ID. NO. 316     5938     GUGGCUU U UAAGGUC   Seq. ID. NO. 317     5939     UGGCUUU U AAGGUCA   Seq. ID. NO. 318     5940     GGCUUUU A AGGUCAU   Seq. ID. NO. 319     5945     UUAAGGU C AUGAGCG   Seq. ID. NO. 320     5965     GCGCCCU C CGCCGAG   Seq. ID. NO. 321     5981     ACCUGGU U AACUUGC   Seq. ID. NO. 322     5982     CCUGGUU A ACUUGCU   Seq. ID. NO. 323     5990     ACUUGCU C CCUGCCA   Seq. ID. NO. 324     6004     AUCCUCU C CCCCGGC   Seq. ID. NO. 325     6020     CCCUGGU C GUCGGGG   Seq. ID. NO. 326     6023     UGGUCGU C GGGGUCG   Seq. ID. NO. 327     6029     UCGGGGU C GUGUGUG   Seq. ID. NO. 328     6044     CAGCAAU C CUGCGUC   Seq. ID. NO. 329     6051     CCUGCGU C GGCACGU   Seq. ID. NO. 330     6106     AUAGCGU U CGCUUCG   Seq. ID. NO. 331     6107     UAGCGUU C GCUUCGC   Seq. ID. NO. 332     6111     GUUCGCU U CGCGGGG   Seq. ID. NO. 333     6413     ACGGCAU C AUGCAAA   Seq. ID. NO. 334     6574     CCGAACU A UUCCAGG   Seq. ID. NO. 335     6576     CAACUAU U CCAGGGC   Seq. ID. NO. 336     6577     AACUAUU C CAGGGCG   Seq. ID. NO. 337     6637     GGGGACU U CCACUAC   Seq. ID. NO. 338     6638     GGGACUU C CACUACG   Seq. ID. NO. 339     6643     UUCCACU A CGUGACG   Seq. ID. NO. 340     6671     ACAACGU A AAAUGCC   Seq. ID. NO. 341     6703     CCCGAAU U CUUCACC   Seq. ID. NO. 342     6704     CCGAAUU C UUCACCG   Seq. ID. NO. 343     6706     CAAUUCU U CACCGAA   Seq. ID. NO. 344     6707     AAUUCUU C ACCGAAU   Seq. ID. NO. 345     6715     ACCGAAU U GGACGGG   Seq. ID. NO. 346     6730     GUGCGGU U GCACAGG   Seq. ID. NO. 347     6739     CACAGGU A CGCUCCG   Seq. ID. NO. 348     6744     GAUCGCU C CGGCGUG   Seq. ID. NO. 349     6759     CAGACCU C UCCUACG   Seq. ID. NO. 350     6761     CACCUCU C CUACGGG   Seq. ID. NO. 351     6764     CUCUCCU A CGGGAGG   Seq. ID. NO. 352     6776     AGGAUGU C ACAUUCC   Seq. ID. NO. 353     6782     UCACAUU C CAGGUCG   Seq. ID. NO. 354     6788     UCCAGGU C GGGCUCA   Seq. ID. NO. 355     6794     UCGGGCU C AACCAAU   Seq. ID. NO. 356     6802     AACCAAU A CCUGGUU   Seq. ID. NO. 357     6809     ACCUGGU U GGGUCAC   Seq. ID. NO. 358     6814     GUUGGGU C ACAGCUC   Seq. ID. NO. 359     6821     CACAGCU C CCAUGCG   Seq. ID. NO. 360     6906     UAAACGU A GGCUGGC   Seq. ID. NO. 361     6922     AGGGGGU C UCCCCCC   Seq. ID. NO. 362     6924     GGGGUCU C CCCCCUC   Seq. ID. NO. 363     6931     CCCCCCU C CUUGGCC   Seq. ID. NO. 364     6934     CCCUCCU U GGCCAGC   Seq. ID. NO. 365     6943     GCCAGCU C UUCAGCU   Seq. ID. NO. 366     6958     AGCCAAU U GUCUGCG   Seq. ID. NO. 367     6961     CAAUUGU C UGCGCCU   Seq. ID. NO. 368     7034     CCAACCU C CUGUGGC   Seq. ID. NO. 369     7118     ACCCGCU U CGAGCGG   Seq. ID. NO. 370     7119     CCCGCUU C GAGCGGA   Seq. ID. NO. 371     7145     GGGAAGU A UCCGUUG   Seq. ID. NO. 372     7195     CCCGCGU U GCCCAUA   Seq. ID. NO. 373     7202     UGCCCAU A UGGGCAC   Seq. ID. NO. 374     7218     CCCGGAU U ACAACCC   Seq. ID. NO. 375     7219     CCGGAUU A CAACCCU   Seq. ID. NO. 376     7234     CCACUGU U AGAGUCC   Seq. ID. NO. 377     7235     CACUGUU A GAGUCCU   Seq. ID. NO. 378     7251     GAAAAGU C CGGACUA   Seq. ID. NO. 379     7258     CCGGACU A CGUCCCU   Seq. ID. NO. 380     7262     ACUACGU C CCUCCGG   Seq. ID. NO. 381     7266     CGUCCCU C CGGCGGU   Seq. ID. NO. 382     7288     UGCCCAU U GCCGCCU   Seq. ID. NO. 383     7296     GCCGCCU A CCACGGG   Seq. ID. NO. 384     7354     ACAGAGU C CACCGUG   Seq. ID. NO. 385     7386     GCUGGCU A CUAAGAC   Seq. ID. NO. 386     7389     GGCUACU A AGACUUU   Seq. ID. NO. 387     7395     UAAGACU U UCGGCAG   Seq. ID. NO. 388     7396     AAGACUU U CGGCAGC   Seq. ID. NO. 389     7397     AGACUUU C GGCAGCU   Seq. ID. NO. 390     7411     UCCGGAU C GUCGGCC   Seq. ID. NO. 391     7414     GGAUCGU C GGCCGUU   Seq. ID. NO. 392     7421     CGGCCGU U GACAGCG   Seq. ID. NO. 393     7498     UCGUACU C CUCCAUG   Seq. ID. NO. 394     7501     UACUCCU C CAUGCCC   Seq. ID. NO. 395     7514     CCCCCCU U GAGGGGG   Seq. ID. NO. 396     7539     CCCUGAU C UCAGCGA   Seq. ID. NO. 397     7541     CUGAUCU C AGCGACG   Seq. ID. NO. 398     7552     GACGGGU C UUGGUCU   Seq. ID. NO. 399     7554     CGGGUCU U GGUCUAC   Seq. ID. NO. 400     7558     UCUUGGU C UACCGUG   Seq. ID. NO. 401     7560     UUGGUCU A CCGUGAG   Seq. ID. NO. 402     7589     ACGACAU C GUCUGCU   Seq. ID. NO. 403     7592     ACAUCGU C UGCUGCU   Seq. ID. NO. 404     7600     UGCUGCU C AAUGUCC   Seq. ID. NO. 405     7606     UCAAUGU C CUACACA   Seq. ID. NO. 406     7667     UGCCCAU C AACGCGU   Seq. ID. NO. 407     7723     ACAACAU C CCGCAGU   Seq. ID. NO. 408     7775     UGCAAGU C CUGGACG   Seq. ID. NO. 409     7789     GACCACU A CCGGGAC   Seq. ID. NO. 410     7839     UAAGGCU A AACUUCU   Seq. ID. NO. 411     7847     AACUUCU A UCCGUAG   Seq. ID. NO. 412     7849     CUUCUAU C CGUAGAA   Seq. ID. NO. 413     7853     UAUCCGU A GAAGAAG   Seq. ID. NO. 414     7894     GCCAAAU C UAAAUUU   Seq. ID. NO. 415     7896     CAAAUCU A AAUUUGG   Seq. ID. NO. 416     7900     UCUAAAU U UGGCUAU   Seq. ID. NO. 417     7901     CUAAAUU U GGCUAUG   Seq. ID. NO. 418     7906     UUUGGCU A UGGGGCA   Seq. ID. NO. 419     7955     ACCACAU C CGCUCCG   Seq. ID. NO. 420     7960     AUCCGCU C CGUGUGG   Seq. ID. NO. 421     8075     CUCGCCU U AUCGUAU   Seq. ID. NO. 422     8076     UCGCCUU A UCGUAUU   Seq. ID. NO. 423     8078     GCCUCGU A CGGAUUC   Seq. ID. NO. 424     8170     UCCUCGU A CGGAUUC   Seq. ID. NO. 425     8176     UACGGAU U CCAGUAC   Seq. ID. NO. 426     8182     UUCCAGU A CUCUCCU   Seq. ID. NO. 427     8187     GUACUCU C CUGGGCA   Seq. ID. NO. 428     8201     AGCGGGU U GAGUUCC   Seq. ID. NO. 429     8206     GUUGAGU U CCUGGUG   Seq. ID. NO. 430     8207     UUGAGUU C CUGGUGA   Seq. ID. NO. 431     8227     UGGAAAU C AAAGAAA   Seq. ID. NO. 432     8357     AGGCCAU A AAGUCGC   Seq. ID. NO. 433     8362     AUAAAGU C GCUCACG   Seq. ID. NO. 434     8366     AGUCGCU C ACGGAGC   Seq. ID. NO. 435     8378     AGCGGCU C UACAUCG   Seq. ID. NO. 436     8380     CGGCUCU A CAUCGGG   Seq. ID. NO. 437     8384     UCUACAU C GGGGGCC   Seq. ID. NO. 438     8424     CUGCGGU U AUCGCCG   Seq. ID. NO. 439     8425     UGCGGUU A UCGCCGG   Seq. ID. NO. 440     8427     CGGUUAU C GCCGGUG   Seq. ID. NO. 441     8460     GACGACU A GCUGCGG   Seq. ID. NO. 442     8508     GGCCUGU C GAGCUGC   Seq. ID. NO. 443     8522     CAAAGCU C CAGGACU   Seq. ID. NO. 444     8540     CGAUGCU C GUGAACG   Seq. ID. NO. 445     8558     ACGACCU U GUCGUUA   Seq. ID. NO. 446     8561     ACCUUGU C GUUAUCU   Seq. ID. NO. 447     8564     UUGUCGU U AUCUGUG   Seq. ID. NO. 448     8638     AGGUACU C UGCCCCC   Seq. ID. NO. 449     8671     CCAGAAU A CGACUUG   Seq. ID. NO. 450     8698     UCAUGCU C CUCCAAC   Seq. ID. NO. 451     8701     UGCUCCU C CAACGUG   Seq. ID. NO. 452     8728     GACGCAU C CGGCAAA   Seq. ID. NO. 453     8774     CCCCCCU U GCACGGG   Seq. ID. NO. 454     8842     AUCAUGU A UGCGCCC   Seq. ID. NO. 455     8854     CCCACCU U AUGGGCA   Seq. ID. NO. 456     8855     CCACCUU A UGGGCAA   Seq. ID. NO. 457     8871     GAUGAUU U UGAUGAC   Seq. ID. NO. 458     8880     GAUGACU C ACUUCUU   Seq. ID. NO. 459     8931     CCUGGAU U GUCAGAU   Seq. ID. NO. 460     8934     GGAUUGU C AGAUCUA   Seq. ID. NO. 461     8939     GUCAGAU C UACGGGG   Seq. ID. NO. 462     8941     CAGAUCU A CGGGGCC   Seq. ID. NO. 463     9065     CAUGCCU C AGGAAAC   Seq. ID. NO. 464     9074     GGAAACU U GGGGUAC   Seq. ID. NO. 465     9080     UUGGGGU A CCGCCCU   Seq. ID. NO. 466     9088     CCGCCCU U GCGAGUC   Seq. ID. NO. 467     9095     UGCGAGU C UGGAGAC   Seq. ID. NO. 468     9119     GAAGUGU C CGCGCUA   Seq. ID. NO. 469     9126     CCGCGCU A GGCUACU   Seq. ID. NO. 470     9131     CUAGGCU A CUGUCCC   Seq. ID. NO. 471     9136     CUACUGU C CCAAGGG   Seq. ID. NO. 472     9226     GCCGCGU C CCAGCUG   Seq. ID. NO. 473     9238     CUGGACU U GUCCAGC   Seq. ID. NO. 474     9241     GACUUGU C CAGCUGG   Seq. ID. NO. 475     9250     AGCUGGU U CGUUGCU   Seq. ID. NO. 476     9251     GCUGGUU C GUUGCUG   Seq. ID. NO. 477     9254     GGUUCGU U GCUGGUU   Seq. ID. NO. 478     9278     GAGACAU A UAUCACA   Seq. ID. NO. 479     9280     GACAUAU A UCACAGC   Seq. ID. NO. 480     9282     CAUAUAU C ACAGCCU   Seq. ID. NO. 481     9292     AGCCUGU C UCGUGCC   Seq. ID. NO. 482     9326     GGUGCCU A CUCCUAC   Seq. ID. NO. 483     9329     GCCUACU C CUACUUU   Seq. ID. NO. 484     9332     UACUCCU A CUUUCCG   Seq. ID. NO. 485     9335     UCCUACU U UCCGUAG   Seq. ID. NO. 486     9336     CCUACUU U CCGUAGG   Seq. ID. NO. 487     9337     CUACUUU C CGUAGGG   Seq. ID. NO. 488     9341     UUUCCGU A GGGGUAG   Seq. ID. NO. 489     9347     UAGGGGU A GGCAUCU   Seq. ID. NO. 490     9353     UAGGCAU C UACCUGC   Seq. ID. NO. 491     9355     GGCAUCU A CCUGCUC   Seq. ID. NO. 492     9362     ACCUGCU C CCCAACC   Seq. ID. NO. 493     9385     GGGAGCU A AUCACUC   Seq. ID. NO. 494     9388     AGCUAAU C ACUCCAG   Seq. ID. NO. 495     9392     AAUCACU C CAGGCCA   Seq. ID. NO. 496     9402     GGCCAAU A GGCCAUC   Seq. ID. NO. 497     ______________________________________      .sup.a Sequences which exhibit perfect homology between the two genomes      are highlighted in bold face type.

Methods for preparation of ribozymes useful in this invention are generally described by Draper, entitled, "Method and Reagent For Treatment of Arthritic Conditions", filed Nov. 12, 1993, and assigned U.S. Ser. No. 08/152,487, the whole of which is hereby incorporated by reference herein.

In a second related aspect, the invention features a mammalian cell which includes an enzymatic RNA molecule as described above. Preferably, the mammalian cell is a human or other primate cell.

In a third related aspect, the invention features an expression vector which includes nucleic acid encoding the enzymatic RNA molecules described above, located in the vector, e.g., in a manner which allows expression of that enzymatic RNA molecule within a mammalian cell.

In a fourth related aspect, the invention features a method for treatment of an HCV-caused disease by administering to a patient an enzymatic RNA molecule which cleaves HCV RNA in the regions discussed above.

The invention provides a class of chemical cleaving agents which exhibit a high degree of specificity for the viral RNA of HCV type infected cells. The ribozyme molecule is preferably targeted to a highly conserved sequence region of HCV such that all types and strains of this virus can be treated with a single ribozyme. Such enzymatic RNA molecules can be delivered exogenously to infected cells. In the preferred hammerhead motif the small size (less than 40 nucleotides, preferably between 32 and 36 nucleotides in length) of the molecule allows the cost of treatment to be reduced compared to other ribozyme motifs.

Synthesis of ribozymes greater than 100 nucleotides in length is very difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. Delivery of ribozymes by expression vectors is primarily feasible using only ex vivo treatments. This limits the utility of this approach. In this invention, small ribozyme motifs (e.g., of the hammerhead structure, shown generally in FIG. 1) are used for exogenous delivery. The simple structure of these molecules also increases the ability of the ribozyme to invade targeted regions of the mRNA structure. Thus, unlike the situation when the hammerhead structure is included within longer transcripts, there are no non-ribozyme flanking sequences to interfere with correct folding of the ribozyme structure or with complementary binding of the ribozyme to the mRNA target region.

The enzymatic RNA molecules of this invention can be used to treat HCV virus infections. Infected animals can be treated at the time of productive infection. This timing of treatment will reduce viral loads in infected cells and disable viral replication in any subsequent rounds of infection. This is possible because the preferred ribozymes disable those structures required for successful initiation of viral protein synthesis. For treatment of transformed hepatocytes, the methods of this invention allow inhibition of the expression of viral genes thought to cause cell transformation.

The preferred targets of the present invention are advantageous over other targets since they do not act only at the time of viral absorption or genomic replication during infection. In addition, viral particles which are released during a first round of infection in the presence of such ribozymes will still be immunogenic by virtue of having their capsids intact. Thus, one method of this invention allows the creation of defective but immunogenic viral particles, and thus a continued possibility of initiation of an immune response in a treated animal.

In addition, the enzymatic RNA molecules of this invention can be used in vitro in a cell culture infected with HCV viruses to produce viral particles which have intact capsids and defective genomic RNA. These particles can then be used for instigation of immune responses in a prophylactic manner, or as a treatment of infected animals.

Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The drawing will first briefly be described.

Drawing

FIG. 1 is a diagrammatic representation of a hammerhead motif ribozyme showing stems I, II and III (marked (I), (II) and (III) respectively) interacting with an HCV target region. The 5' and 3' ends of both ribozyme and target are shown. Dashes indicate base-paired nucleotides.

Target Sites

The genome of HCV may be subject to rapid genetic drift by virtue of its RNA content and the nature of errors in genomic replication. Those regions (genes) of the genome which are essential for virus replication, however, are expected to maintain a constant sequence (i.e., are conserved) over extensive periods of time. These regions are preferred target sites in this invention since they are more likely to be conserved between different types or strains of HCV viruses, and thus only one ribozyme is needed to destroy all such viruses. Thus, one ribozyme may be used to target all HCV viruses. We have selected several such regions in the genomes of these viruses, and examined their nucleotide sequences for the presence of regions which may be cleaved by ribozymes targeted to those regions. One region analyzed in detail is the 5' non-translated region; other regions (such as the C or NS1 protein ORFs) can be analyzed in a manner similar to that described below.

Ribozymes targeting selected regions of the HCV genome are preferably chosen to cleave the target RNA in is a manner which inhibits translation of the RNA. Genes are selected such that such viral replication is inhibited, e.g., by inhibiting protein synthesis. Selection of effective target sites within these critical regions of viral RNA entails testing the accessibility of the target RNA to hybridization with various oligonucleotide probes. These studies can be performed using RNA probes and assaying accessibility by cleaving the hybrid molecule with RNaseH (see below). Alternatively, such a study can use ribozyme probes designed from secondary structure predictions of the RNAs, and assaying cleavage products by polyacrylamide gel electrophoresis (PAGE), to detect the presence of cleaved and uncleaved molecules.

The following is but one example of a method by which suitable target sites can be identified and is not limiting in this invention. Generally, the method involves identifying potential cleavage sites for a hammerhead ribozyme, and then testing each of these sites to determine their suitability as targets by ensuring that secondary structure formation is minimal.

The mRNA sequences of the virus are folded using RNAfold computer analyses. The regions of the mRNA, in this case the 5' nucleotides of the HCV genome, which are predicted to have weak or non-base paired nucleotides are searched for putative ribozyme recognition motifs. These sites represent the preferred sites for hammerhead or other ribozyme cleavage within these target RNAs.

Short RNA substrates corresponding to each of the gene sites are designed. Each substrate is composed of two to three nucleotides at the 5' and 3' ends that will not base pair with a corresponding ribozyme recognition region. The unpaired regions flank a central region of 12-14 nucleotides to which complementary arms in the ribozyme are designed.

The structure of each substrate sequence is predicted using a PC fold computer program. Sequences which give a positive free energy of binding are accepted. Sequences which give a negative free energy are modified by trimming one or two bases from each of the ends. If the modified sequences are still predicted to have a strong secondary structure, they are rejected.

After substrates are chosen, ribozymes are designed to each of the RNA substrates. Ribozyme folding is also analyzed using PC fold.

Ribozyme molecules are sought which form hammerhead motif stem II (see FIG. 1) regions and contain flanking arms which are devoid of intramolecular base pairing. Often the ribozymes are modified by trimming a base from the ends of the ribozyme, or by introducing additional base pairs in stem II to achieve the desired fold. Ribozymes with incorrect folding are rejected. After substrate/ribozyme pairs are found to contain correct intramolecular structures, the molecules are folded together to predict intermolecular interactions. A schematic representation of a ribozyme with its coordinate base pairing to its cognate target sequence is shown in FIG. 1.

Using such analyses, the following predictions of effective target sites in the HCV genomic RNA, based upon computer generated RNA structure analysis, were obtained (see Table 1). The target nucleotide is listed with the genomic nucleotide number (in the HCV genome) given to the left of the sequence. Flanking nucleotides are given for reference.

Those targets thought to be useful as ribozyme targets can be tested to determine accessibility to nucleic acid probes in a ribonuclease H assay (see below). This assay provides a quick test of the use of the target site without requiring synthesis of a ribozyme. It can be used to screen for sites most suited for ribozyme attack.

Synthesis of Ribozymes

Ribozymes useful in this invention can be produced by gene transcription as described by Cech, supra, or by chemical synthesis. Chemical synthesis of RNA is similar to that for DNA synthesis. The additional 2'-OH group in RNA, however, requires a different protecting group strategy to deal with selective 3'-5' internucleotide bond formation, and with RNA susceptibility to degradation in the presence of bases. The recently developed method of RNA synthesis utilizing the t-butyldimethylsilyl group for the protection of the 2' hydroxyl is the most reliable method for synthesis of ribozymes. The method reproducibly yields RNA with the correct 3'-5' internucleotide linkages, with average coupling yields in excess of 99%, and requires only a two-step deprotection of the polymer.

A method based upon H-phosphonate chemistry gives a relatively lower coupling efficiency than a method based upon phosphoramidite chemistry. This is a problem for synthesis of DNA as well. A promising approach to scale-up of automatic oligonucleotide synthesis has been described recently for the H-phosphonates. A combination of a proper coupling time and additional capping of "failure" sequences gave high yields in the synthesis of oligodeoxynucleotides in scales in the range of 14 micromoles with as little as 2 equivalents of a monomer in the coupling step. Another alternative approach is to use soluble polymeric supports (e.g., polyethylene glycols), instead of the conventional solid supports. This method can yield short oligonucleotides in hundred milligram quantities per batch utilizing about 3 equivalents of a monomer in a coupling step.

Various modifications to ribozyme structure can be made to enhance the utility of ribozymes. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such ribozymes to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.

Exogenous delivery of ribozymes benefits from chemical modification of the backbone, e.g., by the overall negative charge of the ribozyme molecule being reduced to facilitate diffusion across the cell membrane. The present strategies for reducing the oligonucleotide charge include: modification of internucleotide linkages by ethylphosphonates, use of phosphoramidites, linking oligonucleotides to positively charged molecules, and creating complex packages composed of oligonucleotides, lipids and specific receptors or effectors for targeted cells. Examples of such modifications include sulfur-containing ribozymes containing phosphorothioates and phosphorodithioates as internucleotide linkages in RNA. Synthesis of such sulfur-modified ribozymes is achieved by use of the sulfur-transfer reagent, ³ H-1,2-benzenedithiol-3-one 1,1-dioxide. Ribozymes may also contain ribose modified ribonucleotides. Pyrimidine analogues are prepared from uridine using a procedure employing diethylamino sulphur trifluoride (DAST) as a starting reagent. Ribozymes can also be either electrostatically or covalently attached to polymeric cations for the purpose of reducing charge. The polymer can be attached to the ribozyme by simply converting the 3'-end to a ribonucleoside dialdehyde which is obtained by a periodate cleavage of the terminal 2',3'-cis diol system. Depending on the specific requirements for delivery systems, other possible modifications may include different linker arms containing carboxyl, amino or thiol functionalities. Yet further examples include use of methylphosphonates and 2'-o-methylribose and 5' or 3' capping or blocking with m₇ GpppG or m₃ ²,2,7 GpppG.

For example, a kinased ribozyme is contacted with guanosine triphosphate and guanyltransferase to add a m³ G cap to the ribozyme. After such synthesis, the ribozyme can be gel purified using standard procedure. To ensure that the ribozyme has the desired activity, it may be tested with and without the 5' cap using standard procedures to assay both its enzymatic activity and its stability.

Synthetic ribozymes, including those containing various modifiers, can be purified by high pressure liquid chromatography (HPLC). Other liquid chromatography techniques, employing reverse phase columns and anion exchangers on silica and polymeric supports may also be used.

There follows an example of the synthesis of one ribozyme. A solid phase phosphoramidite chemistry is employed. Monomers used are 2'-tert-butyl-dimethylsilyl cyanoethylphosphoramidities of uridine, N-benzoylcytosine, N-phenoxyacetyl adenosine and guanosine (Glen Research, Sterling, Va.). Solid phase synthesis is carried out on either an ABI 394 or 380B DNA/RNA synthesizer using the standard protocol provided with each machine. The only exception is that the coupling step is increased from 10 to 12 minutes. The phosphoramidite concentration is 0.1M. Synthesis is done on a 1 μmole scale using a 1 μmole RNA reaction column (Glen Research). The average coupling efficiencies are between 97% and 98% for the 394 model, and between 97% and 99% for the 380B model, as determined by a calorimetric measurement of the released trityl cation.

Blocked ribozymes are cleaved from the solid support (e.g., CPG), and the bases and diphosphoester moiety deprotected in a sterile vial by dry ethanolic ammonia (2 mL) at 55° C. for 16 hours. The reaction mixture is cooled on dry ice. Later, the cold liquid is transferred into a sterile screw cap vial and lyophilized.

To remove the 2'-tert-butyl-dimethylsilyl groups from the ribozyme, the residue is suspended in 1M tetra-n-butylammonium fluoride in dry THF (TBAF), using a 20 fold excess of the reagent for every silyl group, for 16 hours at ambient temperature (about 15°-25° C.). The reaction is quenched by adding an equal volume of sterile 1M triethylamine acetate, pH 6.5. The sample is cooled and concentrated on a SpeedVac to half the initial volume.

The ribozymes are purified in two steps by HPLC on a C4 300μ 5 mm DeltaPak column in an acetonitrile gradient.

The first step, or "trityl on" step, is a separation of 5'-DMT-protected ribozyme(s) from failure sequences lacking a 5'-DMT group. Solvents used for this step are: A (0.1M triethylammonium acetate, pH 6.8) and B (acetonitrile). The elution profile is: 20% B for 10 minutes, followed by a linear gradient of 20% B to 50% B over 50 minutes, 50% B for 10 minutes, a linear gradient of 50% B to 100% B over 10 minutes, and a linear gradient of 100% B to 0% B over 10 minutes.

The second step is a purification of a completely deblocked ribozyme by a treatment of 2% trifluoroacetic acid on a C4 300μ 5 mm DeltaPak column in an acetonitrile gradient. Solvents used for this second step are: A (0.1M Triethylammonium acetate, pH 6.8) and B (80% acetonitrile, 0.1M triethylammonium acetate, pH 6.8). The elution profile is: 5% B for 5 minutes, a linear gradient of 5% B to 15% B over 60 minutes, 15% B for 10 minutes, and a linear gradient of 15% B to 0% B over 10 minutes.

The fraction containing ribozyme is cooled and lyophilized on a SpeedVac. Solid residue is dissolved in a minimum amount of ethanol and sodium perchlorate in acetone. The ribozyme is collected by centrifugation, washed three times with acetone, and lyophilized.

Expression Vector

While synthetic ribozymes are preferred in this invention, those produced by expression vectors can also be used. In designing a suitable ribozyme expression vector the following factors are important to consider. The final ribozyme must be kept as small as possible to minimize unwanted secondary structure within the ribozyme. A promoter (e.g., the human cytomegalovirus immediate early promoter) should be chosen to be a relatively strong promoter, and expressible both in vitro and in vivo. Such a promoter should express the ribozyme at a level suitable to effect production of enough ribozyme to destroy a target RNA, but not at too high a level to prevent other cellular activities from occurring (unless cell death itself is desired).

A hairpin at the 5' end of the ribozyme is useful to protect the ribozyme from 5'-3' exonucleases. A selected hairpin at the 3' end of the ribozyme is useful because it acts as a protection from 3'-5' exonucleases. Such hairpins can be inserted within the vector sequences to allow standard ribozymes to be placed in an appropriate orientation and expressed with such sequences attached.

Poly(A) tails are also useful to protect the 3' end of the ribozyme. These can be provided by either including a poly(A) signal site in the expression vector (to signal a cell to add the poly(A) tail in vivo), or by introducing a poly(A) sequence directly into the expression vector. In the first approach the signal must be located to prevent unwanted secondary structure formation with other parts of the ribozyme. In the second approach, the poly(A) stretch may reduce in size over time when expressed in vivo, and thus the vector may need to be checked over time. Care must be taken in addition of a poly(A) tail which binds poly(A) binding proteins which prevent the ribozyme from acting upon their target sequence.

Ribozyme Testing

Once the desired ribozymes are selected, synthesized and purified, they are tested in kinetic and other experiments to determine their utility. An example of such a procedure is provided below.

Preparation of Ribozyme

Crude synthetic ribozyme (typically 350 μg at a time) is purified by separation on a 15% denaturing polyacrylamide gel (0.75 mm thick, 40 cm long) and visualized by UV shadowing. Once excised, gel slices containing full length ribozyme are soaked in 5 ml gel elution buffer (0.5M NH₄ OAc, 1 mM EDTA) overnight with shaking at 4° C. The eluent is desalted over a C-18 matrix (Sep-Pak cartridges, Millipore, Milford, Mass.) and vacuum dried. The dried RNA is resuspended in 50-100 μl TE (TRIS 10 mM, EDTA 1 mM, pH 7.2). An aliquot of this solution is diluted 100 fold into 1 ml TE, half of which was used to spectrophotometrically quantitate the ribozyme solution. The concentration of this dilute stock is typically 150-800 nM. Purity of the ribozyme is confirmed by the presence of a single band on a denaturing polyacrylamide gel.

A ribozyme may advantageously be synthesized in two or more portions. Each portion of a ribozyme will generally have only limited or no enzymatic activity, and the activity will increase substantially (by at least 5-10 fold) when all portions are ligated (or otherwise juxtaposed) together. A specific example of hammerhead ribozyme synthesis is provided below.

The method involves synthesis of two (or more) shorter "half" ribozymes and ligation of them together using T4 RNA ligase. For example, to make a 34 mer ribozyme, two 17 mers are synthesized, one is phosphorylated, and both are gel purified. These purified 17 mers are then annealed to a DNA splint strand complementary to the two 17 mers. This DNA splint has a sequence designed to locate the two 17 mer portions with one end of each adjacent each other. The juxtaposed RNA molecules are then treated with T4 RNA ligase in the presence of ATP. The 34 mer RNA so formed is then HPLC purified.

Preparation of Substrates

Approximately 10-30 pmoles of unpurified substrate is radioactively 5' end-labelled with T4 polynucleotide kinase using 25 pmoles of Letter to client reaction proposed γ-³² P! ATP. The entire labelling mix is separated on a 20% denaturing polyacrylamide gel and visualized by autoradiography. The full length band is excised and soaked overnight at 4° C. in 100 μl of TE (10 mM Tris-HCl pH 7.6, 0.1MM EDTA).

Kinetics Reactions

For reactions using short substrates (between 8 and 16 bases) a substrate solution is made 1× in assay buffer (75 mM Tris-HCl, pH 7.6; 0.1 mM EDTA, 10 mM MgCl₂) such that the concentration of substrate is less than 1 nM. A ribozyme solution (typically 20 nM) is made 1× in assay buffer and four dilutions are made using 1× assay buffer. Fifteen μl of each ribozyme dilution (i.e., 20, 16, 12, 8 and 4 nM) is placed in a separate tube. These tubes and the substrate tube are pre-incubated at 37° C. for at least five minutes.

The reaction is started by mixing 15 μl of substrate into each ribozyme tube by rapid pipetting (note that final ribozyme concentrations are 10, 8, 6, 4, 2 nM). 5 μl aliquots are removed at 15 or 30 second intervals and quenched with 5 μl stop solution (95% formamide, 20 mM EDTA xylene cyanol, and bromphenol blue dyes). Following the final ribozyme time point, an aliquot of the remaining substrate is removed as a zero ribozyme control.

The samples are separated on either 15% or 20% polyacrylamide gels. Each gel is visualized and quantitated with an Ambis beta scanner (Ambis Systems, San Diego, Calif.).

For the most active ribozymes, kinetic analyses are performed in substrate excess to determine K_(m) and K_(cat) values.

For kinetic reactions with long RNA substrates (greater than 15 bases in length) the substrates are prepared by transcription using T7 RNA polymerase and defined templates containing a T7 promoter, and DNA encoding appropriate nucleotides of the viral RNA. The substrate solution is made 1× in assay buffer (75 mM Tris-HCl, pH 7.6; 0.1 mM EDTA; 10 mM MgCl₂) and contains 58 nanomolar concentration of the long RNA molecules. The reaction is started by addition of gel purified ribozymes to 1 μM concentration. Aliquots are removed at 20, 40, 60, 80 and 100 minutes, then quenched by the addition of 5 μl stop solution. Cleavage products are separated using denaturing PAGE. The bands are visualized and quantitated with an Ambis beta scanner.

Kinetic Analysis

A simple reaction mechanism for ribozyme-mediated cleavage is: ##EQU1## where R=ribozyme, S=substrate, and P=products. The boxed step is important only in substrate excess. Because ribozyme concentration is in excess over substrate concentration, the concentration of the ribozyme-substrate complex ( R:S!) is constant over time except during the very brief time when the complex is being initially formed, i.e.,: ##EQU2## where t=time, and thus:

    (R)(S)k.sub.1 =(RS)(k.sub.2 +k.sub.1)

The rate of the reaction is the rate of disappearance of substrate with time: ##EQU3## Substituting these expressions: ##EQU4## Integrating this expression with respect to time yields: ##EQU5## where S₀ =initial substrate. Therefore, a plot of the negative log of fraction substrate uncut versus time (in minutes) yields a straight line with slope: ##EQU6## where k_(obs) =observed rate constant. A plot of slope (k_(obs)) versus ribozyme concentration yields a straight line with a slope which is: ##EQU7##

Using these equations the data obtained from the kinetic experiments provides the necessary information to determine which ribozyme tested is most useful, or active. Such ribozymes can be selected and tested in in vivo or ex vivo systems.

Liposome Preparation

Lipid molecules are dissolved in a volatile organic solvent (CHCl₃, methanol, diethylether, ethanol, etc.). The organic solvent is removed by evaporation. The lipid is hydrated into suspension with 0.1× phosphate buffered saline (PBS), then freeze-thawed 3× using liquid nitrogen and incubation at room temperature. The suspension is extruded sequentially through a 0.4 μm, 0.2-μm and 0.1 μm polycarbonate filters at maximum pressure of 800 psi. The ribozyme is mixed with the extruded liposome suspension and lyophilized to dryness. The lipid/ribozyme powder is rehydrated with water to one-tenth the original volume. The suspension is diluted to the minimum volume required for extrusion (0.4 ml for 1.5 ml barrel and 1.5 ml for 10 ml barrel) with 1×PBS and re-extruded through 0.4 μm, 0.2 μm, 0.1 μm polycarbonate filters. The liposome entrapped ribozyme is separated from untrapped ribozyme by gel filtration chromatography (SEPHAROSE CL-4B, BIOGEL A5M). The liposome extractions are pooled and sterilized by filtration through a 0.2 μm filter. The free ribozyme is pooled and recovered by ethanol precipitation. The liposome concentration is determined by incorporation of a radioactive lipid. The ribozyme concentration is determined by labeling with ³² P. Rossi et al., 1992 supra (and references cited therein) describe other methods suitable for preparation of liposomes.

In Vivo Assay

The efficacy of action of a chosen ribozyme may be tested in vivo by use of cell cultures sensitive to HCV using standard procedures. For example, monolayer cultures of HCV-sensitive HepG2 cells are grown in 6 or 96 well tissue culture plates. Prior to transduction with HCV expression plasmids, cultures are treated for three to 24 hours with ribozyme-containing liposomes or cationic lipid/ribozyme complexes. Cells are then rinsed with phosphate buffered saline (PBS) and transduced or transfected with HCV expression plasmids. The cells are treated for three to five days with appropriate ribozyme preparations in fresh changes of medium. Total cellular RNA is harvested by the guanidine isothiocyanate technique and the amount of HCV mRNA is quantified and assessed for ribozyme-mediated cleavage using the ribonuclease protection assay. Alternatively, cellular lysates can be prepared and the core particles of HCV could be immunoprecipitated using polyclonal anti-core antiserum adsorbed to protein A-Sepharose according to manufacturers directions. The precipitated cores are treated with ribonuclease to digest any non-encapsidated RNAs and the core protein is digested with proteinase K/phenol extraction. Usually one-half of the total RNA and one-half of the extracted RNA is analyzed using the ribonuclease protection assay.

Ribonuclease Protection Assay

The accumulation of target mRNA in cells or the cleavage of the RNA by ribozymes or RNaseH (in vitro or in vivo) can be quantified using an RNase protection assay.

In this method, antisense riboprobes are transcribed from template DNA using T7 RNA polymerase (U.S. Biochemicals) in 20 μl reactions containing 1× transcription buffer (supplied by the manufacturer), 0.2 mM ATP, GTP and UTP, 1 U/μl pancreatic RNase inhibitor (Boehringer Mannheim Biochemicals) and 200 μCi ³² P-labeled CTP (800 Ci/mmol, New England Nuclear) for 1 h at 37° C. Template DNA is digested with 1 U RNase-free DNase I (U.S. Biochemicals, Cleveland, Ohio.) at 37° C. for 15 minutes and unincorporated nucleotides removed by G-50 SEPHADEX spin chromatography.

In a manner similar to the transcription of antisense probe, the target RNA can be transcribed in vitro using a suitable DNA template. The transcript is purified by standard methods and digested with ribozyme at 37° C. according to methods described later.

Alternatively, virus-infected cells are harvested into 1 ml of PBS, transferred to a 1.5 ml EPPENDORF tube, pelleted for 30 seconds at low speed in a microcentrifuge, and lysed in 70 μl of hybridization buffer (4M guanidine isothiocyanate, 0.1% sarcosyl, 25 mM sodium citrate, pH 7.5). Cell lysate (45 μl) or defined amounts of in vitro transcript (also in hybridization buffer) is then combined with 5 μl of hybridization buffer containing 5×10⁵ cpm of each antisense riboprobe in 0.5 ml EPPENDORF tubes, overlaid with 25 μl mineral oil, and hybridization accomplished by heating overnight at 55° C. The hybridization reactions are diluted into 0.5 ml RNase solution (20 U/ml RNase A, 2 U/ml RNase T1, 10 U/ml RNase-free DNAse I in 0.4M NaCl), heated for 30 minutes at 37° C., and 10 μl of 20% SDS and 10 μl of Proteinase K (10 mg/ml) added, followed by an additional 30 minutes incubation at 37° C. Hybrids are partially purified by extraction with 0.5 ml of a 1:1 mixture of phenol/chloroform; aqueous phases are combined with 0.5 ml isopropanol, and RNase-resistant hybrids pelleted for 10 minutes at room temperature (about 20° C.) in a microcentrifuge. Pellets are dissolved in 10 μl loading buffer (95% formamide, 1× TBE, 0.1% bromophenol blue, 0.1% xylene cylanol), heated to 95° C. for five minutes, cooled on ice, and analyzed on 4% polyacrylamide/7M urea gels under denaturing conditions.

Ribozyme Stability

The chosen ribozyme can be tested to determine its stability, and thus its potential utility. Such a test can also be used to determine the effect of various chemical modifications (e.g., addition of a poly(A) tail) on the ribozyme stability and thus aid selection of a more stable ribozyme. For example, a reaction mixture contains 1 to 5 pmoles of 5' (kinased) and/or 3' labeled ribozyme, 15 μg of cytosolic extract and 2.5 mM MgCl₂ in a total volume of 100 μl. The reaction is incubated at 37° C. Eight μl aliquots are taken at timed intervals and mixed with 8 μl of a stop mix (20 mM EDTA, 95% formamide). Samples are separated on a 15% acrylamide sequencing gel, exposed to film, and scanned with an Ambis.

A 3'-labelled ribozyme can be formed by incorporation of the ³² P-labeled cordycepin at the 3' OH using poly(A) polymerase. For example, the poly(A) polymerase reaction contains 40 mM Tris, pH 8, 10 mM MgCl₂, 250 mM NaCl, 2.5 mM MnCl₂,; 3 μl P³² cordycepin, 500 Ci/mM; and 6 units poly(A) polymerase in a total volume of 50 μl. The reaction mixture was incubated for 30 minutes at 37° C.

Effect of base substitution upon Ribozyme Activity

To determine which primary structural characteristics could change ribozyme cleavage of substrate, minor base changes can be made in the substrate cleavage region recognized by a specific ribozyme. For example, the substrate sequences can be changed at the central "C" nucleotide, changing the cleavage site from a GUC to a GUA motif. The K_(cat) /K_(m) values for cleavage using each substrate are then analyzed to determine if such a change increases ribozyme cleavage rates. Similar experiments can be performed to address the effects of changing bases complementary to the ribozyme binding arms. Changes predicted to maintain strong binding to the complementary substrate are preferred. Minor changes in nucleotide content can alter ribozyme/substrate interactions in ways which are unpredictable based upon binding strength alone. Structures in the catalytic core region of the ribozyme recognize trivial changes in either substrate structure or the three dimensional structure of the ribozyme/substrate complex.

To begin optimizing ribozyme design, the cleavage rates of ribozymes containing varied arm lengths, but targeted to the same length of short RNA substrate can be tested. Minimal arm lengths are required and effective cleavage varies with ribozyme/substrate combinations.

The cleavage activity of selected ribozymes can be assessed using HCV-homologous substrates or HCV genomic RNA. The assays are performed in ribozyme excess and approximate K_(cat) /K_(min) values obtained. Comparison of values obtained with short and long substrates indicates utility in vivo of a ribozyme.

Intracellular Stability of liposome-delivered ribozymes

To test the stability of a chosen ribozyme in vivo the following test is useful. Ribozymes are ³² P-end labeled, entrapped in liposomes and delivered to HCV sensitive cells for three hours. The cells are fractionated and purified by phenol/chloroform extraction. Cells (1×10⁷, T-175 flask) are scraped from the surface of the flask and washed twice with cold PBS. The cells are homogenized by douncing 35 times in 4 ml of TSE (10 mM Tris, pH 7.4, 0.25M Sucrose, mM EDTA). Nuclei are pelleted at 100×g for 10 minutes. Subcellular organelles (the membrane fraction) are pelleted at 200,000×g for two hours using an SW60 rotor. The pellet is resuspended in 1 ml of H buffer (0.25M Sucrose, 50 mM HEPES, pH 7.4) The supernatant contains the cytoplasmic fraction (in approximately 3.7 ml). The nuclear pellet is resuspended in 1 ml of 65% sucrose in TM (50 mM Tris, pH 74., 2.5 mM MgCl₂) and banded on a sucrose step gradient (1 ml nuclei in 65% sucrose TM, 1 ml 60% sucrose TM, 1 ml 55% sucrose TM, 50% sucrose TM, 300 ul 25% sucrose TM) for one hour at 37,000×g with an SW60 rotor. The nuclear band is harvested and diluted to 10% sucrose with TM buffer. Nuclei are pelleted at 37,000×g using an SW60 rotor for 15 minutes and the pellet resuspended in 1 ml of TM buffer. Aliquots are size fractionated on denaturing polyacrylamide gels and the intracellular localization determined. By comparison to the migration rate of newly synthesized ribozyme, the various fraction containing intact ribozyme can be determined.

To investigate modifications which would lengthen the half-life of ribozyme molecules intracellularly, the cells may be fractioned as above and the purity of each fraction assessed by assaying enzyme activity known to exist in that fraction.

The various cell fractions are frozen at -70° C. and used to determine relative nuclease resistances of modified ribozyme molecules. Ribozyme molecules may be synthesized with 5 phosphorothioate (ps), or 2'-O-methyl (2'-OMe) modifications at each end of the molecule. These molecules and a phosphodiester version of the ribozyme are end-labeled with ³² P and ATP using T4 polynucleotide kinase. Equal concentrations are added to the cell cytoplasmic extracts and aliquots of each taken at 10 minute intervals. The samples are size fractionated by denaturing PAGE and relative rates of nuclease resistance analyzed by scanning the gel with an Ambis scanner. The results show whether the ribozymes are digested by the cytoplasmic extract, and which versions are relatively more nuclease resistant. Modified ribozymes generally maintain 80-90% of the catalytic activity of the native ribozyme when short RNA substrates are employed.

Unlabeled, 5' end-labeled or 3' end-labeled ribozymes can be used in the assays. These experiments can also be performed with human cell extracts to verify the observations.

Administration of Ribozyme

Selected ribozymes can be administered prophylactically, or to virus infected patients, e.g., by exogenous delivery of the ribozyme to an infected tissue by means of an appropriate delivery vehicle, e.g., a liposome, a controlled release vehicle, by use of iontophoresis, electroporation or ion paired molecules, or covalently attached adducts, and other pharmacologically approved methods of delivery. Routes of administration include intramuscular, aerosol, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal. Expression vectors for immunization with ribozymes and/or delivery of ribozymes are also suitable. See Draper, U.S. Ser. No. 08/152,487, filed Nov. 12, 1993, the whole of which including drawings is hereby incorporated herein by reference. See, also, Sullivan, U.S. Ser. No. 08/155,474, the whole of which including drawings is hereby incorporated herein by reference.

The specific delivery route of any selected ribozyme will depend on the use of the ribozyme. Generally, a specific delivery program for each ribozyme will focus on naked ribozyme uptake with regard to intracellular localization, followed by demonstration of efficacy. Alternatively, delivery to these same cells in an organ or tissue of an animal can be pursued. Uptake studies will include uptake assays to evaluate cellular ribozyme uptake, regardless of the delivery vehicle or strategy. Such assays will also determine the intracellular localization of the ribozyme following uptake, ultimately establishing the requirements for maintenance of steady-state concentrations within the cellular compartment containing the target sequence (nucleus and/or cytoplasm). Efficacy and cytotoxicity can then be tested. Toxicity will not only include cell viability but also cell function.

Some methods of delivery that may be used include:

a. encapsulation in liposomes,

b. transduction by retroviral vectors,

c. conjugation with cholesterol,

d. localization to nuclear compartment utilizing antigen binding site found on most snRNAs,

e. neutralization of charge of ribozyme by using nucleotide derivatives, and

f. use of blood stem cells to distribute ribozymes throughout the body.

At least three types of delivery strategies are useful in the present invention, including: ribozyme modifications, particle carrier drug delivery vehicles, and viral expression vectors. Unmodified ribozymes and antisense oligonucleotides, like most small molecules, are taken up by cells, albeit slowly. To enhance cellular uptake, the ribozyme may be modified essentially at random, in ways which reduces its charge but maintains specific functional groups. This results in a molecule which is able to diffuse across the cell membrane, thus removing the permeability barrier.

Modification of ribozymes to reduce charge is just one approach to enhance the cellular uptake of these larger molecules. The random approach, however, is not advisable since ribozymes are structurally and functionally more complex than small drug molecules. The structural requirements necessary to maintain ribozyme catalytic activity are well understood by those in the are. These requirements are taken into consideration when designing modifications to enhance cellular delivery. The modifications are also designed to reduce susceptibility to nuclease degradation. Both of these characteristics should greatly improve the efficacy of the ribozyme. Cellular uptake can be increased by several orders of magnitude without having to alter the phosphodiester linkages necessary for ribozyme cleavage activity.

Chemical modifications of the phosphate backbone will reduce the negative charge allowing free diffusion across the membrane. This principle has been successfully demonstrated for antisense DNA technology. The similarities in chemical composition between DNA and RNA make this a feasible approach. In the body, maintenance of an external concentration will be necessary to drive the diffusion of the modified ribozyme into the cells of the tissue. Administration routes which allow the diseased tissue to be exposed to a transient high concentration of the drug, which is slowly dissipated by systemic adsorption are preferred. Intravenous administration with a drug carrier designed to increase the circulation half-life of the ribozyme can be used. The size and composition of the drug carrier restricts rapid clearance from the blood stream. The carrier, made to accumulate at the site of infection, can protect the ribozyme from degradative processes.

Drug delivery vehicles are effective for both systemic and topical administration. They can be designed to serve as a slow release reservoir, or to deliver their contents directly to the target cell. An advantage of using direct delivery drug vehicles is that multiple molecules are delivered per uptake. Such vehicles have been shown to increase the circulation half-life of drugs which would otherwise be rapidly cleared from the blood stream. Some examples of such specialized drug delivery vehicles which fall into this category are liposomes, hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres.

From this category of delivery systems, liposomes are preferred. Liposomes increase intracellular stability, increase uptake efficiency and improve biological activity.

Liposomes are hollow spherical vesicles composed of lipids arranged in a similar fashion as those lipids which make up the cell membrane. They have an internal aqueous space for entrapping water soluble compounds and range in size from 0.05 to several microns in diameter. Several studies have shown that liposomes can deliver RNA to cells and that the RNA remains biologically active.

For example, a liposome delivery vehicle originally designed as a research tool, Lipofectin, has been shown to deliver intact mRNA molecules to cells yielding production of the corresponding protein.

Liposomes offer several advantages: They are non-toxic and biodegradable in composition; they display long circulation half-lives; and recognition molecules can be readily attached to their surface for targeting to tissues. Finally, cost effective manufacture of liposome-based pharmaceuticals, either in a liquid suspension or lyophilized product, has demonstrated the viability of this technology as an acceptable drug delivery system.

Other controlled release drug delivery systems, such as nonoparticles and hydrogels may be potential delivery vehicles for a ribozyme. These carriers have been developed for chemotherapeutic agents and protein-based pharmaceuticals, and consequently, can be adapted for ribozyme delivery.

Topical administration of ribozymes is advantageous since it allows localized concentration at the site of administration with minimal systemic adsorption. This simplifies the delivery strategy of the ribozyme to the disease site and reduces the extent of toxicological characterization. Furthermore, the amount of material to be applied is far less than that required for other administration routes. Effective delivery requires the ribozyme to diffuse into the infected cells. Chemical modification of the ribozyme to neutralize negative charge may be all that is required for penetration. However, in the event that charge neutralization is insufficient, the modified ribozyme can be co-formulated with permeability enhancers, such as Azone or oleic acid, in a liposome. The liposomes can either represent a slow release presentation vehicle in which the modified ribozyme and permeability enhancer transfer from the liposome into the infected cell, or the liposome phospholipids can participate directly with the modified ribozyme and permeability enhancer in facilitating cellular delivery. In some cases, both the ribozyme and permeability enhancer can be formulated into a suppository formulation for slow release.

Ribozymes may also be systemically administered. Systemic absorption refers to the accumulation of drugs in the blood stream followed by distribution throughout the entire body. Administration routes which lead to systemic absorption include: intravenous, subcutaneous, intraperitoneal, intranasal, intrathecal and ophthalmic. Each of these administration routes expose the ribozyme to an accessible diseased tissue. Subcutaneous administration drains into a localized lymph node which proceeds through the lymphatic network into the circulation. The rate of entry into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier localizes the ribozyme at the lymph node. The ribozyme can be modified to diffuse into the cell, or the liposome can directly participate in the delivery of either the unmodified or modified ribozyme to the cell.

Intraperitoneal administration also leads to entry into the circulation, with once again, the molecular weight or size controlling the rate of entry.

Liposomes injected intravenously show accumulation in the liver, lung and spleen. The composition and size can be adjusted so that this accumulation represents 30% to 40% of the injected dose. The rest is left to circulate in the blood stream for up to 24 hours.

The chosen method of delivery should result in cytoplasmic accumulation and molecules should have some nuclease-resistance for optimal dosing. Nuclear delivery may be used but is less preferable. Most preferred delivery methods include liposomes (10-400 nm), hydrogels, controlled-release polymers, microinjection or electroporation (for ex vivo treatments) and other pharmaceutically applicable vehicles. The dosage will depend upon the disease indication and the route of administration but should be between 100-200 mg/kg of body weight/day. The duration of treatment will extend through the course of the disease symptoms, usually at least 14-16 days and possibly continuously. Multiple daily doses are anticipated for topical applications, ocular applications and vaginal applications. The number of doses will depend upon disease delivery vehicle and efficacy data from clinical trials.

Establishment of therapeutic levels of ribozyme within the cell is dependent upon the rate of uptake and degradation. Decreasing the degree of degradation will prolong the intracellular half-life of the ribozyme. Thus, chemically modified ribozymes, e.g., with modification of the phosphate backbone, or capping of the 5' and 3' ends of the ribozyme with nucleotide analogs may require different dosaging. Descriptions of useful systems are provided in the art cited above, all of which is hereby incorporated by reference herein.

The claimed ribozymes are also useful as diagnostic tools to specifically or non-specifically detect the presence of a target RNA in a sample. That is, the target RNA, if present in the sample, will be specifically cleaved by the ribozyme, and thus can be readily and specifically detected as smaller RNA species. The presence of such smaller RNA species is indicative of the presence of the target RNA in the sample.

Other embodiments are within the following claims.

    __________________________________________________________________________     SEQUENCE LISTING     (1) GENERAL INFORMATION:     (iii) NUMBER OF SEQUENCES: 497     (2) INFORMATION FOR SEQ ID NO: 1:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 1:     CGACACUCCACCAUA15     (2) INFORMATION FOR SEQ ID NO: 2:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 2:     GCAGCCUCCAGGACC15     (2) INFORMATION FOR SEQ ID NO: 3:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 3:     CCCCCCUCCCGGGAG15     (2) INFORMATION FOR SEQ ID NO: 4:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 4:     UAGUGGUCUGCGGAA15     (2) INFORMATION FOR SEQ ID NO: 5:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 5:     GGUGAGUACACCGGA15     (2) INFORMATION FOR SEQ ID NO: 6:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 6:     CCGGAAUUGCCAGGA15     (2) INFORMATION FOR SEQ ID NO: 7:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 7:     CCUUUCUUGGAUCAA15     (2) INFORMATION FOR SEQ ID NO: 8:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 8:     ACCCGCUCAAUGCCU15     (2) INFORMATION FOR SEQ ID NO: 9:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 9:     GACUGCUAGCCGAGU15     (2) INFORMATION FOR SEQ ID NO: 10:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 10:     GCCGAGUAGUGUUGG15     (2) INFORMATION FOR SEQ ID NO: 11:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 11:     GUAGUGUUGGGUCGC15     (2) INFORMATION FOR SEQ ID NO: 12:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 12:     GUUGGGUCGCGAAAG15     (2) INFORMATION FOR SEQ ID NO: 13:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 13:     UUGUGGUACUGCCUG15     (2) INFORMATION FOR SEQ ID NO: 14:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 14:     GCCUGAUAGGGUGCU15     (2) INFORMATION FOR SEQ ID NO: 15:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 15:     GGGUGCUUGCGAGUG15     (2) INFORMATION FOR SEQ ID NO: 16:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 16:     GGGAGGUCUCGUAGA15     (2) INFORMATION FOR SEQ ID NO: 17:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 17:     GAGGUCUCGUAGACC15     (2) INFORMATION FOR SEQ ID NO: 18:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 18:     GUCUCGUAGACCGUG15     (2) INFORMATION FOR SEQ ID NO: 19:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 19:     AGGACGUCAAGUUCC15     (2) INFORMATION FOR SEQ ID NO: 20:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 20:     GUCAAGUUCCCGGGC15     (2) INFORMATION FOR SEQ ID NO: 21:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 21:     UCAAGUUCCCGGGCG15     (2) INFORMATION FOR SEQ ID NO: 22:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 22:     CGGUGGUCAGAUCGU15     (2) INFORMATION FOR SEQ ID NO: 23:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 23:     CCCACGUUGGGUGUG15     (2) INFORMATION FOR SEQ ID NO: 24:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 24:     CGCGACUAGGAAGAC15     (2) INFORMATION FOR SEQ ID NO: 25:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 25:     GAAGACUUCCGAACG15     (2) INFORMATION FOR SEQ ID NO: 26:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 26:     AAGACUUCCGAACGG15     (2) INFORMATION FOR SEQ ID NO: 27:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 27:     GAACGGUCGCAACCU15     (2) INFORMATION FOR SEQ ID NO: 28:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 28:     ACAACCUAUCCCCAA15     (2) INFORMATION FOR SEQ ID NO: 29:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 29:     AACCUAUCCCCAAGG15     (2) INFORMATION FOR SEQ ID NO: 30:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 30:     CAAGGCUCGCCGACC15     (2) INFORMATION FOR SEQ ID NO: 31:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 31:     CGAGGGUAGGGCCUG15     (2) INFORMATION FOR SEQ ID NO: 32:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 32:     CUGGGCUCAGCCUGG15     (2) INFORMATION FOR SEQ ID NO: 33:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 33:     CCUGGGUACCCUUGG15     (2) INFORMATION FOR SEQ ID NO: 34:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 34:     GUACCCUUGGCCCCU15     (2) INFORMATION FOR SEQ ID NO: 35:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 35:     GGCCCCUCUAUGGCA15     (2) INFORMATION FOR SEQ ID NO: 36:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 36:     CCCCUCUAUGGCAAU15     (2) INFORMATION FOR SEQ ID NO: 37:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 37:     GAUGGCUCCUGUCAC15     (2) INFORMATION FOR SEQ ID NO: 38:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 38:     CUCCUGUCACCCCGC15     (2) INFORMATION FOR SEQ ID NO: 39:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 39:     CGCGGCUCCCGGCCU15     (2) INFORMATION FOR SEQ ID NO: 40:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 40:     CCGGCCUAGUUGGGG15     (2) INFORMATION FOR SEQ ID NO: 41:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 41:     GCCUAGUUGGGGCCC15     (2) INFORMATION FOR SEQ ID NO: 42:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 42:     GCGCAAUCUGGGUAA15     (2) INFORMATION FOR SEQ ID NO: 43:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 43:     GUAAGGUCAUCGAUA15     (2) INFORMATION FOR SEQ ID NO: 44:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 44:     AGGUCAUCGAUACCC15     (2) INFORMATION FOR SEQ ID NO: 45:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 45:     CAUCGAUACCCUCAC15     (2) INFORMATION FOR SEQ ID NO: 46:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 46:     UGCGGCUUCGCCGAC15     (2) INFORMATION FOR SEQ ID NO: 47:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 47:     GCGGCUUCGCCGACC15     (2) INFORMATION FOR SEQ ID NO: 48:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 48:     AUGGGGUACAUUCCG15     (2) INFORMATION FOR SEQ ID NO: 49:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 49:     GGUACAUUCCGCUCG15     (2) INFORMATION FOR SEQ ID NO: 50:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 50:     GUACAUUCCGCUCGU15     (2) INFORMATION FOR SEQ ID NO: 51:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 51:     UUCCGCUCGUCGGCG15     (2) INFORMATION FOR SEQ ID NO: 52:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 52:     CGCUCGUCGGCGCCC15     (2) INFORMATION FOR SEQ ID NO: 53:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 53:     CCCCCCUAGGGGGCG15     (2) INFORMATION FOR SEQ ID NO: 54:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 54:     AUGGUGUCCGGGUUC15     (2) INFORMATION FOR SEQ ID NO: 55:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 55:     UCCGGGUUCUGGAGG15     (2) INFORMATION FOR SEQ ID NO: 56:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 56:     CCGGGUUCUGGAGGA15     (2) INFORMATION FOR SEQ ID NO: 57:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 57:     GUGAACUACGCAACA15     (2) INFORMATION FOR SEQ ID NO: 58:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 58:     GGGAACUUGCCCGGU15     (2) INFORMATION FOR SEQ ID NO: 59:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 59:     GCCCGGUUGCUCUUU15     (2) INFORMATION FOR SEQ ID NO: 60:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 60:     GGUUGCUCUUUCUCU15     (2) INFORMATION FOR SEQ ID NO: 61:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 61:     AUUGUGUAUGAGGCA15     (2) INFORMATION FOR SEQ ID NO: 62:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 62:     GCAUGAUCAUGCAUA15     (2) INFORMATION FOR SEQ ID NO: 63:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 63:     GGUGCGUACCCUGCG15     (2) INFORMATION FOR SEQ ID NO: 64:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 64:     CCUGCGUUCGGGAGA15     (2) INFORMATION FOR SEQ ID NO: 65:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 65:     CUGCGUUCGGGAGAA15     (2) INFORMATION FOR SEQ ID NO: 66:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 66:     AACGCCUCCCGUUGU15     (2) INFORMATION FOR SEQ ID NO: 67:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 67:     CUCCCGUUGUUGGGU15     (2) INFORMATION FOR SEQ ID NO: 68:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 68:     CCGUUGUUGGGUAGC15     (2) INFORMATION FOR SEQ ID NO: 69:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 69:     GUUGGGUAGCGCUCA15     (2) INFORMATION FOR SEQ ID NO: 70:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 70:     GCCACGUCGACUUGC15     (2) INFORMATION FOR SEQ ID NO: 71:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 71:     GUCGACUUGCUCGUU15     (2) INFORMATION FOR SEQ ID NO: 72:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 72:     ACUUGCUCGUUGGGG15     (2) INFORMATION FOR SEQ ID NO: 73:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 73:     UGCUCGUUGGGGCGG15     (2) INFORMATION FOR SEQ ID NO: 74:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 74:     GCCGCUUUCUGUUCC15     (2) INFORMATION FOR SEQ ID NO: 75:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 75:     CCGCUUUCUGUUCCG15     (2) INFORMATION FOR SEQ ID NO: 76:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 76:     UUUCUGUUCCGCCAU15     (2) INFORMATION FOR SEQ ID NO: 77:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 77:     UUCUGUUCCGCCAUG15     (2) INFORMATION FOR SEQ ID NO: 78:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 78:     GCCAUGUACGUGGGG15     (2) INFORMATION FOR SEQ ID NO: 79:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 79:     UGCGGAUCCGUUUUC15     (2) INFORMATION FOR SEQ ID NO: 80:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 80:     GAUCCGUUUUCCUCG15     (2) INFORMATION FOR SEQ ID NO: 81:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 81:     AUCCGUUUUCCUCGU15     (2) INFORMATION FOR SEQ ID NO: 82:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 82:     UCCGUUUUCCUCGUC15     (2) INFORMATION FOR SEQ ID NO: 83:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 83:     CCGUUUUCCUCGUCU15     (2) INFORMATION FOR SEQ ID NO: 84:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 84:     GCCAUGUAUCAGGUC15     (2) INFORMATION FOR SEQ ID NO: 85:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 85:     CAUGUAUCAGGUCAC15     (2) INFORMATION FOR SEQ ID NO: 86:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 86:     AUCAGGUCACCGCAU15     (2) INFORMATION FOR SEQ ID NO: 87:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 87:     AAGCUGUCGUGGAUA15     (2) INFORMATION FOR SEQ ID NO: 88:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 88:     CGUGGAUAUGGUGGC15     (2) INFORMATION FOR SEQ ID NO: 89:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 89:     GGGGAGUCCUAGCGG15     (2) INFORMATION FOR SEQ ID NO: 90:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 90:     GAGUCCUAGCGGGCC15     (2) INFORMATION FOR SEQ ID NO: 91:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 91:     CGGGCCUUGCCUACU15     (2) INFORMATION FOR SEQ ID NO: 92:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 92:     CUUGCCUACUAUUCC15     (2) INFORMATION FOR SEQ ID NO: 93:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 93:     GCCUACUAUUCCAUG15     (2) INFORMATION FOR SEQ ID NO: 94:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 94:     CUACUAUUCCAUGGU15     (2) INFORMATION FOR SEQ ID NO: 95:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 95:     UACUAUUCCAUGGUG15     (2) INFORMATION FOR SEQ ID NO: 96:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 96:     GCUCCAUCGACAAGU15     (2) INFORMATION FOR SEQ ID NO: 97:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 97:     GACAAGUUCGCUCAG15     (2) INFORMATION FOR SEQ ID NO: 98:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 98:     ACAAGUUCGCUCAGG15     (2) INFORMATION FOR SEQ ID NO: 99:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 99:     GUUCGCUCAGGGAUG15     (2) INFORMATION FOR SEQ ID NO: 100:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 100:     GCCCCAUCACCUAUA15     (2) INFORMATION FOR SEQ ID NO: 101:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 101:     AUCACCUAUACCGAG15     (2) INFORMATION FOR SEQ ID NO: 102:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 102:     AGGCCUUACUGCUGG15     (2) INFORMATION FOR SEQ ID NO: 103:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 103:     CUGGCAUUACGCACC15     (2) INFORMATION FOR SEQ ID NO: 104:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 104:     UGGCAUUACGCACCU15     (2) INFORMATION FOR SEQ ID NO: 105:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 105:     CGCACCUCGGCAGUG15     (2) INFORMATION FOR SEQ ID NO: 106:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 106:     GUGUGGUAUCGUACC15     (2) INFORMATION FOR SEQ ID NO: 107:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 107:     GUGGUAUCGUACCUG15     (2) INFORMATION FOR SEQ ID NO: 108:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 108:     GUAUCGUACCUGCGU15     (2) INFORMATION FOR SEQ ID NO: 109:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 109:     CCUGCGUCGCAGGUG15     (2) INFORMATION FOR SEQ ID NO: 110:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 110:     GUGUGGUCCAGUGUA15     (2) INFORMATION FOR SEQ ID NO: 111:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 111:     GCCCUGUUGUAGUGG15     (2) INFORMATION FOR SEQ ID NO: 112:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 112:     CUGUUGUAGUGGGGA15     (2) INFORMATION FOR SEQ ID NO: 113:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 113:     GACCGAUCGGUCCGG15     (2) INFORMATION FOR SEQ ID NO: 114:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 114:     GAUCGGUCCGGUGCC15     (2) INFORMATION FOR SEQ ID NO: 115:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 115:     UGCCCCUACGUAUAA15     (2) INFORMATION FOR SEQ ID NO: 116:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 116:     CCUACGUAUAACUGG15     (2) INFORMATION FOR SEQ ID NO: 117:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 117:     UACGUAUAACUGGGG15     (2) INFORMATION FOR SEQ ID NO: 118:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 118:     AACUGGUUUGGCUGU15     (2) INFORMATION FOR SEQ ID NO: 119:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 119:     ACUGGUUUGGCUGUA15     (2) INFORMATION FOR SEQ ID NO: 120:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 120:     UGGCUGUACAUGGAU15     (2) INFORMATION FOR SEQ ID NO: 121:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 121:     GGGCCCUCCGUGCAA15     (2) INFORMATION FOR SEQ ID NO: 122:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 122:     GCAACAUCGGGGGGG15     (2) INFORMATION FOR SEQ ID NO: 123:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 123:     GGGGGGUCGGCAACC15     (2) INFORMATION FOR SEQ ID NO: 124:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 124:     GCAACCUCACCUUGA15     (2) INFORMATION FOR SEQ ID NO: 125:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 125:     CUCACCUUGACCUGC15     (2) INFORMATION FOR SEQ ID NO: 126:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 126:     GGCCACUUACACAAA15     (2) INFORMATION FOR SEQ ID NO: 127:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 127:     GCCACUUACACAAAA15     (2) INFORMATION FOR SEQ ID NO: 128:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 128:     UGUGGCUCGGGGCCA15     (2) INFORMATION FOR SEQ ID NO: 129:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 129:     CCAUGGUUAACACCU15     (2) INFORMATION FOR SEQ ID NO: 130:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 130:     CAUGGUUAACACCUA15     (2) INFORMATION FOR SEQ ID NO: 131:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 131:     UUACCAUCUUUAAGG15     (2) INFORMATION FOR SEQ ID NO: 132:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 132:     ACCAUCUUUAAGGUU15     (2) INFORMATION FOR SEQ ID NO: 133:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 133:     ACAGGCUUAGUGCUG15     (2) INFORMATION FOR SEQ ID NO: 134:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 134:     CAGGCUUAGUGCUGC15     (2) INFORMATION FOR SEQ ID NO: 135:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 135:     AGAGCGUUGCGACCU15     (2) INFORMATION FOR SEQ ID NO: 136:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 136:     GACAGAUCGGAGCUC15     (2) INFORMATION FOR SEQ ID NO: 137:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 137:     CGGAGCUCAGCCCGC15     (2) INFORMATION FOR SEQ ID NO: 138:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 138:     CUGCUGUCCACGACA15     (2) INFORMATION FOR SEQ ID NO: 139:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 139:     UCCACCUCCAUCAGA15     (2) INFORMATION FOR SEQ ID NO: 140:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 140:     CCUCCAUCAGAACAU15     (2) INFORMATION FOR SEQ ID NO: 141:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 141:     AGAACAUCGUGGACG15     (2) INFORMATION FOR SEQ ID NO: 142:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 142:     CGCGCGUCUGUGCCU15     (2) INFORMATION FOR SEQ ID NO: 143:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 143:     CCGCCCUAGAGAACC15     (2) INFORMATION FOR SEQ ID NO: 144:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 144:     UGGUGGUCCUCAACG15     (2) INFORMATION FOR SEQ ID NO: 145:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 145:     UGGUCCUCAACGCGG15     (2) INFORMATION FOR SEQ ID NO: 146:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 146:     GCCUGGUACAUCAAG15     (2) INFORMATION FOR SEQ ID NO: 147:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 147:     GGUACAUCAAGGGCA15     (2) INFORMATION FOR SEQ ID NO: 148:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 148:     GGCUGGUCCCUGGGG15     (2) INFORMATION FOR SEQ ID NO: 149:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 149:     GCGGCAUAUGCUCUG15     (2) INFORMATION FOR SEQ ID NO: 150:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 150:     AUAUGCUCUGUACGG15     (2) INFORMATION FOR SEQ ID NO: 151:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 151:     GCUCUGUACGGCGUG15     (2) INFORMATION FOR SEQ ID NO: 152:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 152:     UCCUGCUCCUGCUGG15     (2) INFORMATION FOR SEQ ID NO: 153:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 153:     ACGGGCUUACGCCAU15     (2) INFORMATION FOR SEQ ID NO: 154:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 154:     CGGGCUUACGCCAUG15     (2) INFORMATION FOR SEQ ID NO: 155:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 155:     UGGUGGUUACAAUAC15     (2) INFORMATION FOR SEQ ID NO: 156:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 156:     GGUGGUUACAAUACU15     (2) INFORMATION FOR SEQ ID NO: 157:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 157:     UUACAAUACUUUAUC15     (2) INFORMATION FOR SEQ ID NO: 158:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 158:     CAAUACUUUAUCACC15     (2) INFORMATION FOR SEQ ID NO: 159:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 159:     AAUACUUUAUCACCA15     (2) INFORMATION FOR SEQ ID NO: 160:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 160:     GGCGCAUUUGUGCGU15     (2) INFORMATION FOR SEQ ID NO: 161:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 161:     GCGCAUUUGUGCGUG15     (2) INFORMATION FOR SEQ ID NO: 162:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 162:     UGUGGGUCCCCCCUC15     (2) INFORMATION FOR SEQ ID NO: 163:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 163:     CCCCCCUCUCAAUGU15     (2) INFORMATION FOR SEQ ID NO: 164:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 164:     CCCCUCUCAAUGUCC15     (2) INFORMATION FOR SEQ ID NO: 165:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 165:     UCAAUGUCCGGGGGG15     (2) INFORMATION FOR SEQ ID NO: 166:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 166:     CGAUGCUAUCAUCCU15     (2) INFORMATION FOR SEQ ID NO: 167:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 167:     AUGCUAUCAUCCUCC15     (2) INFORMATION FOR SEQ ID NO: 168:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 168:     CUAUCAUCCUCCUCA15     (2) INFORMATION FOR SEQ ID NO: 169:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 169:     UCAUCCUCCUCACAU15     (2) INFORMATION FOR SEQ ID NO: 170:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 170:     UCCUCCUCACAUGUG15     (2) INFORMATION FOR SEQ ID NO: 171:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 171:     CUGCCAUAACUGCGA15     (2) INFORMATION FOR SEQ ID NO: 172:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 172:     AGGCCAUUACGUCCA15     (2) INFORMATION FOR SEQ ID NO: 173:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 173:     GGCCAUUACGUCCAA15     (2) INFORMATION FOR SEQ ID NO: 174:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 174:     AUUACGUCCAAAUGG15     (2) INFORMATION FOR SEQ ID NO: 175:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 175:     AUGGCCUUCAUGAAG15     (2) INFORMATION FOR SEQ ID NO: 176:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 176:     UGGCCUUCAUGAAGC15     (2) INFORMATION FOR SEQ ID NO: 177:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 177:     CCCCGCUACAGGAUU15     (2) INFORMATION FOR SEQ ID NO: 178:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 178:     ACAGGAUUGGGCCCA15     (2) INFORMATION FOR SEQ ID NO: 179:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 179:     CGGGCCUACGAGACC15     (2) INFORMATION FOR SEQ ID NO: 180:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 180:     GAGACCUUGCGGUGG15     (2) INFORMATION FOR SEQ ID NO: 181:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 181:     AGCCCGUCGUCUUCU15     (2) INFORMATION FOR SEQ ID NO: 182:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 182:     CCGUCGUCUUCUCUG15     (2) INFORMATION FOR SEQ ID NO: 183:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 183:     GUCGUCUUCUCUGAC15     (2) INFORMATION FOR SEQ ID NO: 184:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 184:     CCAAGAUCAUCACCU15     (2) INFORMATION FOR SEQ ID NO: 185:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 185:     AGAUCAUCACCUGGG15     (2) INFORMATION FOR SEQ ID NO: 186:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 186:     GGGACAUCAUCUUGG15     (2) INFORMATION FOR SEQ ID NO: 187:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 187:     ACAUCAUCUUGGGAC15     (2) INFORMATION FOR SEQ ID NO: 188:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 188:     AUCAUCUUGGGACUG15     (2) INFORMATION FOR SEQ ID NO: 189:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 189:     UGCCCGUCUCCGCCC15     (2) INFORMATION FOR SEQ ID NO: 190:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 190:     CCCGUCUCCGCCCGA15     (2) INFORMATION FOR SEQ ID NO: 191:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 191:     GGGAGAUACUUCUGG15     (2) INFORMATION FOR SEQ ID NO: 192:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 192:     GGCGACUCCUUGCCC15     (2) INFORMATION FOR SEQ ID NO: 193:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 193:     GACUCCUUGCCCCCA15     (2) INFORMATION FOR SEQ ID NO: 194:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 194:     CCCCCAUCACGGCCU15     (2) INFORMATION FOR SEQ ID NO: 195:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 195:     CUAGCCUCACAGGCC15     (2) INFORMATION FOR SEQ ID NO: 196:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 196:     GGGAGGUUCAAGUGG15     (2) INFORMATION FOR SEQ ID NO: 197:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 197:     GGAGGUUCAAGUGGU15     (2) INFORMATION FOR SEQ ID NO: 198:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 198:     AAGUGGUUUCCACCG15     (2) INFORMATION FOR SEQ ID NO: 199:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 199:     AGUGGUUUCCACCGC15     (2) INFORMATION FOR SEQ ID NO: 200:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 200:     GUGGUUUCCACCGCA15     (2) INFORMATION FOR SEQ ID NO: 201:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 201:     UGUGUGUUGGACCGU15     (2) INFORMATION FOR SEQ ID NO: 202:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 202:     GCCGGCUCAAAGACC15     (2) INFORMATION FOR SEQ ID NO: 203:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 203:     AGACCCUAGCCGGCC15     (2) INFORMATION FOR SEQ ID NO: 204:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 204:     UGCGCCUCCCGGGGC15     (2) INFORMATION FOR SEQ ID NO: 205:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 205:     GGCGCGUUCCCUUAC15     (2) INFORMATION FOR SEQ ID NO: 206:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 206:     GCGCGUUCCCUUACA15     (2) INFORMATION FOR SEQ ID NO: 207:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 207:     GUUCCCUUACACCAU15     (2) INFORMATION FOR SEQ ID NO: 208:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 208:     UUCCCUUACACCAUG15     (2) INFORMATION FOR SEQ ID NO: 209:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 209:     GGUAGCUCGGACCUC15     (2) INFORMATION FOR SEQ ID NO: 210:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 210:     CGGACCUCUAUCUGG15     (2) INFORMATION FOR SEQ ID NO: 211:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 211:     GACCUCUAUCUGGUC15     (2) INFORMATION FOR SEQ ID NO: 212:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 212:     CCUCUAUCUGGUCAC15     (2) INFORMATION FOR SEQ ID NO: 213:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 213:     AUCUGGUCACGAGAC15     (2) INFORMATION FOR SEQ ID NO: 214:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 214:     ACGUCAUUCCGGUGC15     (2) INFORMATION FOR SEQ ID NO: 215:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 215:     CGUCAUUCCGGUGCG15     (2) INFORMATION FOR SEQ ID NO: 216:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 216:     UGACGGUCGGGGGAG15     (2) INFORMATION FOR SEQ ID NO: 217:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 217:     GGAGCCUACUGUCCC15     (2) INFORMATION FOR SEQ ID NO: 218:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 218:     CUACUGUCCCCCAGA15     (2) INFORMATION FOR SEQ ID NO: 219:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 219:     GGCUCUUCGGGUGGC15     (2) INFORMATION FOR SEQ ID NO: 220:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 220:     CACUGCUCUGCCCUU15     (2) INFORMATION FOR SEQ ID NO: 221:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 221:     CUGCCCUUCGGGGCA15     (2) INFORMATION FOR SEQ ID NO: 222:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 222:     UGCCCUUCGGGGCAC15     (2) INFORMATION FOR SEQ ID NO: 223:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 223:     ACGCUGUAGGCAUCU15     (2) INFORMATION FOR SEQ ID NO: 224:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 224:     UAGGCAUCUUCCGGG15     (2) INFORMATION FOR SEQ ID NO: 225:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 225:     GGCAUCUUCCGGGCU15     (2) INFORMATION FOR SEQ ID NO: 226:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 226:     GCAUCUUCCGGGCUG15     (2) INFORMATION FOR SEQ ID NO: 227:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 227:     GGGGGGUUGCGAAGG15     (2) INFORMATION FOR SEQ ID NO: 228:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 228:     GAGCACUAAAGUGCC15     (2) INFORMATION FOR SEQ ID NO: 229:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 229:     GCUGCGUACGCAGCC15     (2) INFORMATION FOR SEQ ID NO: 230:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 230:     CAAGGGUACAAGGUA15     (2) INFORMATION FOR SEQ ID NO: 231:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 231:     CAUCUGUUGCCGCCA15     (2) INFORMATION FOR SEQ ID NO: 232:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 232:     CCAACAUCAGAACUG15     (2) INFORMATION FOR SEQ ID NO: 233:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 233:     CUGGGGUAAGGACCA15     (2) INFORMATION FOR SEQ ID NO: 234:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 234:     UCCACCUAUGGUAAG15     (2) INFORMATION FOR SEQ ID NO: 235:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 235:     CUAUGGUAAGUUCCU15     (2) INFORMATION FOR SEQ ID NO: 236:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 236:     GGUAAGUUCCUUGCC15     (2) INFORMATION FOR SEQ ID NO: 237:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 237:     GUAAGUUCCUUGCCG15     (2) INFORMATION FOR SEQ ID NO: 238:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 238:     AGUUCCUUGCCGACG15     (2) INFORMATION FOR SEQ ID NO: 239:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 239:     AUAUCAUAAUAUGUG15     (2) INFORMATION FOR SEQ ID NO: 240:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 240:     UCAUAAUAUGUGAUG15     (2) INFORMATION FOR SEQ ID NO: 241:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 241:     GCACAGUCCUGGACC15     (2) INFORMATION FOR SEQ ID NO: 242:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 242:     CGCGGCUCGUCGUGC15     (2) INFORMATION FOR SEQ ID NO: 243:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 243:     GGCUCGUCGUGCUCG15     (2) INFORMATION FOR SEQ ID NO: 244:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 244:     UCGUGCUCGCCACCG15     (2) INFORMATION FOR SEQ ID NO: 245:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 245:     CCCAAAUAUUGAGGA15     (2) INFORMATION FOR SEQ ID NO: 246:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 246:     GCUCUGUCCAACACU15     (2) INFORMATION FOR SEQ ID NO: 247:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 247:     GAGAGAUCCCCUUCU15     (2) INFORMATION FOR SEQ ID NO: 248:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 248:     AGGCCAUCCCCCUCG15     (2) INFORMATION FOR SEQ ID NO: 249:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 249:     UCCCCCUCGAGGCCA15     (2) INFORMATION FOR SEQ ID NO: 250:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 250:     AGGCCAUCAAGGGGG15     (2) INFORMATION FOR SEQ ID NO: 251:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 251:     UGCCACUCCAAGAAG15     (2) INFORMATION FOR SEQ ID NO: 252:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 252:     UCGGAAUCAAUGCCG15     (2) INFORMATION FOR SEQ ID NO: 253:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 253:     AUGCCGUAGCGUAUU15     (2) INFORMATION FOR SEQ ID NO: 254:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 254:     GUAGCGUAUUACCGG15     (2) INFORMATION FOR SEQ ID NO: 255:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 255:     AGCGUAUUACCGGGG15     (2) INFORMATION FOR SEQ ID NO: 256:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 256:     GCGUAUUACCGGGGU15     (2) INFORMATION FOR SEQ ID NO: 257:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 257:     UGUCCGUCAUACCGA15     (2) INFORMATION FOR SEQ ID NO: 258:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 258:     CCGUCAUACCGACUA15     (2) INFORMATION FOR SEQ ID NO: 259:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 259:     ACCGACUAGCGGAGA15     (2) INFORMATION FOR SEQ ID NO: 260:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 260:     ACGGGCUACACCGGU15     (2) INFORMATION FOR SEQ ID NO: 261:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 261:     CGGUGAUCGACUGCA15     (2) INFORMATION FOR SEQ ID NO: 262:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 262:     GCGGUGUCGCGCUCA15     (2) INFORMATION FOR SEQ ID NO: 263:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 263:     UCGCGCUCACAACGG15     (2) INFORMATION FOR SEQ ID NO: 264:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 264:     CUGUGCUUGGUAUGA15     (2) INFORMATION FOR SEQ ID NO: 265:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 265:     GCUUGGUAUGAGCUC15     (2) INFORMATION FOR SEQ ID NO: 266:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 266:     AUGAGCUCACGCCCG15     (2) INFORMATION FOR SEQ ID NO: 267:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 267:     UGAGACUACAGUCAG15     (2) INFORMATION FOR SEQ ID NO: 268:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 268:     CUACAGUCAGGUUGC15     (2) INFORMATION FOR SEQ ID NO: 269:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 269:     GUCAGGUUGCGGGCU15     (2) INFORMATION FOR SEQ ID NO: 270:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 270:     GCGGGCUUACCUGAA15     (2) INFORMATION FOR SEQ ID NO: 271:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 271:     CGGGCUUACCUGAAU15     (2) INFORMATION FOR SEQ ID NO: 272:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 272:     CCUGAAUACACCAGG15     (2) INFORMATION FOR SEQ ID NO: 273:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 273:     CCAGGGUUGCCCGUC15     (2) INFORMATION FOR SEQ ID NO: 274:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 274:     UGCCCGUCUGCCAGG15     (2) INFORMATION FOR SEQ ID NO: 275:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 275:     GGACCAUCUGGAGUU15     (2) INFORMATION FOR SEQ ID NO: 276:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 276:     ACCUGGUAGCAUACC15     (2) INFORMATION FOR SEQ ID NO: 277:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 277:     GUAGCAUACCAAGCC15     (2) INFORMATION FOR SEQ ID NO: 278:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 278:     CAGGGCUCAGGCUCC15     (2) INFORMATION FOR SEQ ID NO: 279:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 279:     CUGCUGUAUAGGCUA15     (2) INFORMATION FOR SEQ ID NO: 280:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 280:     GCUGUAUAGGCUAGG15     (2) INFORMATION FOR SEQ ID NO: 281:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 281:     UGGAGGUCGUCACUA15     (2) INFORMATION FOR SEQ ID NO: 282:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 282:     AGGUCGUCACUAGCA15     (2) INFORMATION FOR SEQ ID NO: 283:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 283:     CGUCACUAGCACCUG15     (2) INFORMATION FOR SEQ ID NO: 284:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 284:     UGCUGGUAGGCGGAG15     (2) INFORMATION FOR SEQ ID NO: 285:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 285:     GCGGAGUCCUUGCAG15     (2) INFORMATION FOR SEQ ID NO: 286:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 286:     GAGUCCUUGCAGCUC15     (2) INFORMATION FOR SEQ ID NO: 287:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 287:     GCCGCAUAUUGCCUG15     (2) INFORMATION FOR SEQ ID NO: 288:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 288:     CGCAUAUUGCCUGAC15     (2) INFORMATION FOR SEQ ID NO: 289:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 289:     AACCGGUAGUGUGGU15     (2) INFORMATION FOR SEQ ID NO: 290:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 290:     GUAGGAUCAUUUUGU15     (2) INFORMATION FOR SEQ ID NO: 291:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 291:     CGGCUGUUGUUCCCG15     (2) INFORMATION FOR SEQ ID NO: 292:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 292:     CUGUUGUUCCCGACA15     (2) INFORMATION FOR SEQ ID NO: 293:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 293:     UGUUGUUCCCGACAG15     (2) INFORMATION FOR SEQ ID NO: 294:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 294:     GAGCAGUUCAAGCAG15     (2) INFORMATION FOR SEQ ID NO: 295:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 295:     AGCAGUUCAAGCAGA15     (2) INFORMATION FOR SEQ ID NO: 296:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 296:     CGCUGCUCCCGUGGU15     (2) INFORMATION FOR SEQ ID NO: 297:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 297:     GUGGAGUCCAGGUGG15     (2) INFORMATION FOR SEQ ID NO: 298:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 298:     GGGCCCUUGAGGCCU15     (2) INFORMATION FOR SEQ ID NO: 299:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 299:     GAGGCCUUCUGGGCA15     (2) INFORMATION FOR SEQ ID NO: 300:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 300:     AGGCCUUCUGGGCAA15     (2) INFORMATION FOR SEQ ID NO: 301:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 301:     GCAGGCUUAUCCACU15     (2) INFORMATION FOR SEQ ID NO: 302:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 302:     CAGGCUUAUCCACUC15     (2) INFORMATION FOR SEQ ID NO: 303:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 303:     CUCCUGUUCAACAUC15     (2) INFORMATION FOR SEQ ID NO: 304:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 304:     UCCUGUUCAACAUCU15     (2) INFORMATION FOR SEQ ID NO: 305:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 305:     CUCAACUCGCUCCUC15     (2) INFORMATION FOR SEQ ID NO: 306:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 306:     ACUCGCUCCUCCCAG15     (2) INFORMATION FOR SEQ ID NO: 307:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 307:     GCUGCUUCGGCCUUC15     (2) INFORMATION FOR SEQ ID NO: 308:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 308:     UCGGCCUUCGUGGGC15     (2) INFORMATION FOR SEQ ID NO: 309:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 309:     CGGCCUUCGUGGGCG15     (2) INFORMATION FOR SEQ ID NO: 310:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 310:     CCGGCAUUGCCGGUG15     (2) INFORMATION FOR SEQ ID NO: 311:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 311:     CGGCCAUUGGCAGCA15     (2) INFORMATION FOR SEQ ID NO: 312:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 312:     GCAGCAUAGGCCUUG15     (2) INFORMATION FOR SEQ ID NO: 313:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 313:     UAGGCCUUGGGAAGG15     (2) INFORMATION FOR SEQ ID NO: 314:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 314:     GCGGGCUAUGGAGCG15     (2) INFORMATION FOR SEQ ID NO: 315:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 315:     GUGCACUCGUGGCUU15     (2) INFORMATION FOR SEQ ID NO: 316:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 316:     CGUGGCUUUUAAGGU15     (2) INFORMATION FOR SEQ ID NO: 317:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 317:     GUGGCUUUUAAGGUC15     (2) INFORMATION FOR SEQ ID NO: 318:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 318:     UGGCUUUUAAGGUCA15     (2) INFORMATION FOR SEQ ID NO: 319:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 319:     GGCUUUUAAGGUCAU15     (2) INFORMATION FOR SEQ ID NO: 320:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 320:     UUAAGGUCAUGAGCG15     (2) INFORMATION FOR SEQ ID NO: 321:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 321:     GCGCCCUCCGCCGAG15     (2) INFORMATION FOR SEQ ID NO: 322:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 322:     ACCUGGUUAACUUGC15     (2) INFORMATION FOR SEQ ID NO: 323:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 323:     CCUGGUUAACUUGCU15     (2) INFORMATION FOR SEQ ID NO: 324:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 324:     ACUUGCUCCCUGCCA15     (2) INFORMATION FOR SEQ ID NO: 325:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 325:     AUCCUCUCCCCCGGC1     (2) INFORMATION FOR SEQ ID NO: 326:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 326:     CCCUGGUCGUCGGGG15     (2) INFORMATION FOR SEQ ID NO: 327:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 327:     UGGUCGUCGGGGUCG15     (2) INFORMATION FOR SEQ ID NO: 328:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 328:     UCGGGGUCGUGUGUG15     (2) INFORMATION FOR SEQ ID NO: 329:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 329:     CAGCAAUCCUGCGUC15     (2) INFORMATION FOR SEQ ID NO: 330:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 330:     CCUGCGUCGGCACGU15     (2) INFORMATION FOR SEQ ID NO: 331:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 331:     AUAGCGUUCGCUUCG15     (2) INFORMATION FOR SEQ ID NO: 332:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 332:     UAGCGUUCGCUUCGC15     (2) INFORMATION FOR SEQ ID NO: 333:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 333:     GUUCGCUUCGCGGGG15     (2) INFORMATION FOR SEQ ID NO: 334:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 334:     ACGGCAUCAUGCAAA15     (2) INFORMATION FOR SEQ ID NO: 335:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 335:     CCGAACUAUUCCAGG15     (2) INFORMATION FOR SEQ ID NO: 336:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 336:     GAACUAUUCCAGGGC15     (2) INFORMATION FOR SEQ ID NO: 337:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 337:     AACUAUUCCAGGGCG15     (2) INFORMATION FOR SEQ ID NO: 338:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 338:     GGGGACUUCCACUAC15     (2) INFORMATION FOR SEQ ID NO: 339:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 339:     GGGACUUCCACUACG15     (2) INFORMATION FOR SEQ ID NO: 340:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 340:     UUCCACUACGUGACG15     (2) INFORMATION FOR SEQ ID NO: 341:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 341:     ACAACGUAAAAUGCC15     (2) INFORMATION FOR SEQ ID NO: 342:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 342:     CCCGAAUUCUUCACC15     (2) INFORMATION FOR SEQ ID NO: 343:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 343:     CCGAAUUCUUCACCG15     (2) INFORMATION FOR SEQ ID NO: 344:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 344:     GAAUUCUUCACCGAA15     (2) INFORMATION FOR SEQ ID NO: 345:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 345:     AAUUCUUCACCGAAU15     (2) INFORMATION FOR SEQ ID NO: 346:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 346:     ACCGAAUUGGACGGG15     (2) INFORMATION FOR SEQ ID NO: 347:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 347:     GUGCGGUUGCACAGG15     (2) INFORMATION FOR SEQ ID NO: 348:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 348:     CACAGGUACGCUCCG15     (2) INFORMATION FOR SEQ ID NO: 349:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 349:     GUACGCUCCGGCGUG15     (2) INFORMATION FOR SEQ ID NO: 350:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 350:     CAGACCUCUCCUACG15     (2) INFORMATION FOR SEQ ID NO: 351:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 351:     GACCUCUCCUACGGG15     (2) INFORMATION FOR SEQ ID NO: 352:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 352:     CUCUCCUACGGGAGG15     (2) INFORMATION FOR SEQ ID NO: 353:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 353:     AGGAUGUCACAUUCC15     (2) INFORMATION FOR SEQ ID NO: 354:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 354:     UCACAUUCCAGGUCG15     (2) INFORMATION FOR SEQ ID NO: 355:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 355:     UCCAGGUCGGGCUCA15     (2) INFORMATION FOR SEQ ID NO: 356:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 356:     UCGGGCUCAACCAAU15     (2) INFORMATION FOR SEQ ID NO: 357:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 357:     AACCAAUACCUGGUU15     (2) INFORMATION FOR SEQ ID NO: 358:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 358:     ACCUGGUUGGGUCAC15     (2) INFORMATION FOR SEQ ID NO: 359:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 359:     GUUGGGUCACAGCUC15     (2) INFORMATION FOR SEQ ID NO: 360:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 360:     CACAGCUCCCAUGCG15     (2) INFORMATION FOR SEQ ID NO: 361:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 361:     UAAACGUAGGCUGGC15     (2) INFORMATION FOR SEQ ID NO: 362:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 362:     AGGGGGUCUCCCCCC15     (2) INFORMATION FOR SEQ ID NO: 363:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 363:     GGGGUCUCCCCCCUC15     (2) INFORMATION FOR SEQ ID NO: 364:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 364:     CCCCCCUCCUUGGCC15     (2) INFORMATION FOR SEQ ID NO: 365:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 365:     CCCUCCUUGGCCAGC15     (2) INFORMATION FOR SEQ ID NO: 366:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 366:     GCCAGCUCUUCAGCU15     (2) INFORMATION FOR SEQ ID NO: 367:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 367:     AGCCAAUUGUCUGCG15     (2) INFORMATION FOR SEQ ID NO: 368:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 368:     CAAUUGUCUGCGCCU15     (2) INFORMATION FOR SEQ ID NO: 369:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 369:     CCAACCUCCUGUGGC15     (2) INFORMATION FOR SEQ ID NO: 370:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 370:     ACCCGCUUCGAGCGG15     (2) INFORMATION FOR SEQ ID NO: 371:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 371:     CCCGCUUCGAGCGGA15     (2) INFORMATION FOR SEQ ID NO: 372:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 372:     GGGAAGUAUCCGUUG15     (2) INFORMATION FOR SEQ ID NO: 373:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 373:     CCCGCGUUGCCCAUA15     (2) INFORMATION FOR SEQ ID NO: 374:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 374:     UGCCCAUAUGGGCAC15     (2) INFORMATION FOR SEQ ID NO: 375:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 375:     CCCGGAUUACAACCC15     (2) INFORMATION FOR SEQ ID NO: 376:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 376:     CCGGAUUACAACCCU15     (2) INFORMATION FOR SEQ ID NO: 377:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 377:     CCACUGUUAGAGUCC15     (2) INFORMATION FOR SEQ ID NO: 378:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 378:     CACUGUUAGAGUCCU15     (2) INFORMATION FOR SEQ ID NO: 379:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 379:     GAAAAGUCCGGACUA15     (2) INFORMATION FOR SEQ ID NO: 380:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 380:     CCGGACUACGUCCCU15     (2) INFORMATION FOR SEQ ID NO: 381:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 381:     ACUACGUCCCUCCGG15     (2) INFORMATION FOR SEQ ID NO: 382:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 382:     CGUCCCUCCGGCGGU15     (2) INFORMATION FOR SEQ ID NO: 383:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 383:     UGCCCAUUGCCGCCU15     (2) INFORMATION FOR SEQ ID NO: 384:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 384:     GCCGCCUACCACGGG15     (2) INFORMATION FOR SEQ ID NO: 385:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 385:     ACAGAGUCCACCGUG15     (2) INFORMATION FOR SEQ ID NO: 386:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 386:     GCUGGCUACUAAGAC15     (2) INFORMATION FOR SEQ ID NO: 387:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 387:     GGCUACUAAGACUUU15     (2) INFORMATION FOR SEQ ID NO: 388:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 388:     UAAGACUUUCGGCAG15     (2) INFORMATION FOR SEQ ID NO: 389:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 389:     AAGACUUUCGGCAGC15     (2) INFORMATION FOR SEQ ID NO: 390:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 390:     AGACUUUCGGCAGCU15     (2) INFORMATION FOR SEQ ID NO: 391:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 391:     UCCGGAUCGUCGGCC15     (2) INFORMATION FOR SEQ ID NO: 392:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 392:     GGAUCGUCGGCCGUU15     (2) INFORMATION FOR SEQ ID NO: 393:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 393:     CGGCCGUUGACAGCG15     (2) INFORMATION FOR SEQ ID NO: 394:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 394:     UCGUACUCCUCCAUG15     (2) INFORMATION FOR SEQ ID NO: 395:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 395:     UACUCCUCCAUGCCC15     (2) INFORMATION FOR SEQ ID NO: 396:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 396:     CCCCCCUUGAGGGGG15     (2) INFORMATION FOR SEQ ID NO: 397:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 397:     CCCUGAUCUCAGCGA15     (2) INFORMATION FOR SEQ ID NO: 398:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 398:     CUGAUCUCAGCGACG15     (2) INFORMATION FOR SEQ ID NO: 399:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 399:     GACGGGUCUUGGUCU15     (2) INFORMATION FOR SEQ ID NO: 400:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 400:     CGGGUCUUGGUCUAC15     (2) INFORMATION FOR SEQ ID NO: 401:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 401:     UCUUGGUCUACCGUG15     (2) INFORMATION FOR SEQ ID NO: 402:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 402:     UUGGUCUACCGUGAG15     (2) INFORMATION FOR SEQ ID NO: 403:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 403:     ACGACAUCGUCUGCU15     (2) INFORMATION FOR SEQ ID NO: 404:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 404:     ACAUCGUCUGCUGCU15     (2) INFORMATION FOR SEQ ID NO: 405:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 405:     UGCUGCUCAAUGUCC15     (2) INFORMATION FOR SEQ ID NO: 406:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 406:     UCAAUGUCCUACACA15     (2) INFORMATION FOR SEQ ID NO: 407:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 407:     UGCCCAUCAACGCGU15     (2) INFORMATION FOR SEQ ID NO: 408:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 408:     ACAACAUCCCGCAGU15     (2) INFORMATION FOR SEQ ID NO: 409:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 409:     UGCAAGUCCUGGACG15     (2) INFORMATION FOR SEQ ID NO: 410:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 410:     GACCACUACCGGGAC15     (2) INFORMATION FOR SEQ ID NO: 411:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 411:     UAAGGCUAAACUUCU15     (2) INFORMATION FOR SEQ ID NO: 412:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 412:     AACUUCUAUCCGUAG15     (2) INFORMATION FOR SEQ ID NO: 413:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 413:     CUUCUAUCCGUAGAA15     (2) INFORMATION FOR SEQ ID NO: 414:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 414:     UAUCCGUAGAAGAAG15     (2) INFORMATION FOR SEQ ID NO: 415:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 415:     GCCAAAUCUAAAUUU15     (2) INFORMATION FOR SEQ ID NO: 416:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 416:     CAAAUCUAAAUUUGG15     (2) INFORMATION FOR SEQ ID NO: 417:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 417:     UCUAAAUUUGGCUAU15     (2) INFORMATION FOR SEQ ID NO: 418:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 418:     CUAAAUUUGGCUAUG15     (2) INFORMATION FOR SEQ ID NO: 419:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 419:     UUUGGCUAUGGGGCA15     (2) INFORMATION FOR SEQ ID NO: 420:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 420:     ACCACAUCCGCUCCG15     (2) INFORMATION FOR SEQ ID NO: 421:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 421:     AUCCGCUCCGUGUGG15     (2) INFORMATION FOR SEQ ID NO: 422:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 422:     CUCGCCUUAUCGUAU15     (2) INFORMATION FOR SEQ ID NO: 423:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 423:     UCGCCUUAUCGUAUU15     (2) INFORMATION FOR SEQ ID NO: 424:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 424:     GCCUUAUCGUAUUCC15     (2) INFORMATION FOR SEQ ID NO: 425:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 425:     UCCUCGUACGGAUUC15     (2) INFORMATION FOR SEQ ID NO: 426:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 426:     UACGGAUUCCAGUAC15     (2) INFORMATION FOR SEQ ID NO: 427:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 427:     UUCCAGUACUCUCCU15     (2) INFORMATION FOR SEQ ID NO: 428:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 428:     GUACUCUCCUGGGCA15     (2) INFORMATION FOR SEQ ID NO: 429:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 429:     AGCGGGUUGAGUUCC15     (2) INFORMATION FOR SEQ ID NO: 430:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 430:     GUUGAGUUCCUGGUG15     (2) INFORMATION FOR SEQ ID NO: 431:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 431:     UUGAGUUCCUGGUGA15     (2) INFORMATION FOR SEQ ID NO: 432:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 432:     UGGAAAUCAAAGAAA15     (2) INFORMATION FOR SEQ ID NO: 433:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 433:     AGGCCAUAAAGUCGC15     (2) INFORMATION FOR SEQ ID NO: 434:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 434:     AUAAAGUCGCUCACG15     (2) INFORMATION FOR SEQ ID NO: 435:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 435:     AGUCGCUCACGGAGC15     (2) INFORMATION FOR SEQ ID NO: 436:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 436:     AGCGGCUCUACAUCG15     (2) INFORMATION FOR SEQ ID NO: 437:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 437:     CGGCUCUACAUCGGG15     (2) INFORMATION FOR SEQ ID NO: 438:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 438:     UCUACAUCGGGGGCC15     (2) INFORMATION FOR SEQ ID NO: 439:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 439:     CUGCGGUUAUCGCCG15     (2) INFORMATION FOR SEQ ID NO: 440:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 440:     UGCGGUUAUCGCCGG15     (2) INFORMATION FOR SEQ ID NO: 441:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 441:     CGGUUAUCGCCGGUG15     (2) INFORMATION FOR SEQ ID NO: 442:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 442:     GACGACUAGCUGCGG15     (2) INFORMATION FOR SEQ ID NO: 443:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 443:     GGCCUGUCGAGCUGC15     (2) INFORMATION FOR SEQ ID NO: 444:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 444:     CAAAGCUCCAGGACU15     (2) INFORMATION FOR SEQ ID NO: 445:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 445:     CGAUGCUCGUGAACG15     (2) INFORMATION FOR SEQ ID NO: 446:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 446:     ACGACCUUGUCGUUA15     (2) INFORMATION FOR SEQ ID NO: 447:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 447:     ACCUUGUCGUUAUCU15     (2) INFORMATION FOR SEQ ID NO: 448:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 448:     UUGUCGUUAUCUGUG15     (2) INFORMATION FOR SEQ ID NO: 449:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 449:     AGGUACUCUGCCCCC15     (2) INFORMATION FOR SEQ ID NO: 450:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 450:     CCAGAAUACGACUUG15     (2) INFORMATION FOR SEQ ID NO: 451:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 451:     UCAUGCUCCUCCAAC15     (2) INFORMATION FOR SEQ ID NO: 452:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 452:     UGCUCCUCCAACGUG15     (2) INFORMATION FOR SEQ ID NO: 453:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 453:     GACGCAUCCGGCAAA15     (2) INFORMATION FOR SEQ ID NO: 454:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 454:     CCCCCCUUGCACGGG15     (2) INFORMATION FOR SEQ ID NO: 455:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 455:     AUCAUGUAUGCGCCC15     (2) INFORMATION FOR SEQ ID NO: 456:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 456:     CCCACCUUAUGGGCA15     (2) INFORMATION FOR SEQ ID NO: 457:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 457:     CCACCUUAUGGGCAA15     (2) INFORMATION FOR SEQ ID NO: 458:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 458:     GAUGAUUUUGAUGAC15     (2) INFORMATION FOR SEQ ID NO: 459:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 459:     GAUGACUCACUUCUU15     (2) INFORMATION FOR SEQ ID NO: 460:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 460:     CCUGGAUUGUCAGAU15     (2) INFORMATION FOR SEQ ID NO: 461:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 461:     GGAUUGUCAGAUCUA15     (2) INFORMATION FOR SEQ ID NO: 462:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 462:     GUCAGAUCUACGGGG15     (2) INFORMATION FOR SEQ ID NO: 463:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 463:     CAGAUCUACGGGGCC15     (2) INFORMATION FOR SEQ ID NO: 464:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 464:     CAUGCCUCAGGAAAC15     (2) INFORMATION FOR SEQ ID NO: 465:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 465:     GGAAACUUGGGGUAC15     (2) INFORMATION FOR SEQ ID NO: 466:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 466:     UUGGGGUACCGCCCU15     (2) INFORMATION FOR SEQ ID NO: 467:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 467:     CCGCCCUUGCGAGUC15     (2) INFORMATION FOR SEQ ID NO: 468:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 468:     UGCGAGUCUGGAGAC15     (2) INFORMATION FOR SEQ ID NO: 469:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 469:     GAAGUGUCCGCGCUA15     (2) INFORMATION FOR SEQ ID NO: 470:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 470:     CCGCGCUAGGCUACU15     (2) INFORMATION FOR SEQ ID NO: 471:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 471:     CUAGGCUACUGUCCC15     (2) INFORMATION FOR SEQ ID NO: 472:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 472:     CUACUGUCCCAAGGG15     (2) INFORMATION FOR SEQ ID NO: 473:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 473:     GCCGCGUCCCAGCUG15     (2) INFORMATION FOR SEQ ID NO: 474:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 474:     CUGGACUUGUCCAGC15     (2) INFORMATION FOR SEQ ID NO: 475:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 475:     GACUUGUCCAGCUGG15     (2) INFORMATION FOR SEQ ID NO: 476:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 476:     AGCUGGUUCGUUGCU15     (2) INFORMATION FOR SEQ ID NO: 477:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 477:     GCUGGUUCGUUGCUG15     (2) INFORMATION FOR SEQ ID NO: 478:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 478:     GGUUCGUUGCUGGUU15     (2) INFORMATION FOR SEQ ID NO: 479:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 479:     GAGACAUAUAUCACA15     (2) INFORMATION FOR SEQ ID NO: 480:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 480:     GACAUAUAUCACAGC15     (2) INFORMATION FOR SEQ ID NO: 481:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 481:     CAUAUAUCACAGCCU15     (2) INFORMATION FOR SEQ ID NO: 482:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 482:     AGCCUGUCUCGUGCC15     (2) INFORMATION FOR SEQ ID NO: 483:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 483:     GGUGCCUACUCCUAC15     (2) INFORMATION FOR SEQ ID NO: 484:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 484:     GCCUACUCCUACUUU15     (2) INFORMATION FOR SEQ ID NO: 485:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 485:     UACUCCUACUUUCCG15     (2) INFORMATION FOR SEQ ID NO: 486:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 486:     UCCUACUUUCCGUAG15     (2) INFORMATION FOR SEQ ID NO: 487:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 487:     CCUACUUUCCGUAGG15     (2) INFORMATION FOR SEQ ID NO: 488:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 488:     CUACUUUCCGUAGGG15     (2) INFORMATION FOR SEQ ID NO: 489:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 489:     UUUCCGUAGGGGUAG15     (2) INFORMATION FOR SEQ ID NO: 490:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 490:     UAGGGGUAGGCAUCU15     (2) INFORMATION FOR SEQ ID NO: 491:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 491:     UAGGCAUCUACCUGC15     (2) INFORMATION FOR SEQ ID NO: 492:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 492:     GGCAUCUACCUGCUC15     (2) INFORMATION FOR SEQ ID NO: 493:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 493:     ACCUGCUCCCCAACC15     (2) INFORMATION FOR SEQ ID NO: 494:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 494:     GGGAGCUAAUCACUC15     (2) INFORMATION FOR SEQ ID NO: 495:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 495:     AGCUAAUCACUCCAG15     (2) INFORMATION FOR SEQ ID NO: 496:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 496:     AAUCACUCCAGGCCA15     (2) INFORMATION FOR SEQ ID NO: 497:     (i) SEQUENCE CHARACTERISTICS:     (A) LENGTH: 15     (B) TYPE: nucleic acid     (C) STRANDEDNESS: single     (D) TOPOLOGY: linear     (ii) SEQUENCE DESCRIPTION: SEQ ID NO: 497:     GGCCAAUAGGCCAUC15     __________________________________________________________________________ 

I claim:
 1. An enzymatic RNA molecule which specifically cleaves RNA encoding hepatitis C Virus (HCV) RNA, wherein said enzymatic RNA molecule comprises a substrate binding site and a nucleotide sequence within or surrounding said substrate binding site wherein said nucleotide sequence imparts to said enzymatic RNA molecule activity for the cleavage of said HCV RNA.
 2. The enzymatic RNA molecule of claim 1, wherein said substrate binding site is complementary to said HCV RNA.
 3. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is in a hammerhead motif.
 4. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is in a hairpin motif.
 5. The enzymatic RNA molecule of claim 1, wherein said substrate binding site comprises between 12 and 100 nucleotides complementary to said HCV RNA.
 6. The enzymatic RNA molecule of claim 1, wherein said substrate binding site comprises between 14 and 24 nucleotides complementary to said HCV RNA.
 7. An expression vector comprising nucleic acid sequence encoding one or more enzymatic RNA molecule of claim 1 in a manner which allows expression of said enzymatic RNA molecules.
 8. The expression vector of claim 7, wherein said expression vector is a viral vector.
 9. The expression vector of claim 8, wherein said viral vector is a retrovirus vector.
 10. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is chemically synthesized.
 11. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is in a purified form.
 12. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is active in the presence of divalent metal ions.
 13. The enzymatic RNA molecule of claim 12, wherein said divalent metal ion is magnesium.
 14. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule comprises a ribose modification.
 15. The expression vector of claim 7, wherein said nucleic acid sequence encoding said enzymatic RNA molecule is under the control of a mammalian transcription promoter.
 16. The expression vector of claim 15, wherein said mammalian transcription promoter is a cytomegalovirus promoter.
 17. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule comprises a 5'-cap.
 18. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule comprises a 3'-cap.
 19. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule comprises a 3'-polyA tail.
 20. A method of cleaving HCV RNA comprising the step of contacting said HCV RNA with the enzymatic RNA molecule of claim 1 under conditions suitable for the cleavage of said HCV RNA.
 21. The enzymatic RNA molecule of claim 1, wherein said enzymatic RNA molecule is capable of inhibiting replication of HCV.
 22. The enzymatic RNA molecule of claim 21, wherein said enzymatic RNA molecule is in a hammerhead motif. 